[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Cancer Research UK\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":393},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,12,0,[8,80,117,153,183,217,237,256,276,295,329,365],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":29,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":72,"completionDateStruct":74,"leadSponsor":76,"locationsCount":79},"100494800","phase-2-determine-determining-extended-therapeutic-indications-for-existing-drugs-in-rare-molecularly-defined-indications-using-a-national-evaluation-platform-trial---master-screening-protocol-100494800",false,"NCT05722886","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations","DETERMINE","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED.\n\nCore Inclusion Criteria:\n\n1. Any patient (adult patients or children and TYA as defined in each treatment arm appendix) with histologically proven locally advanced or metastatic cancer (solid tumour or haematological malignancy) who has:\n\n   1. exhausted (or declined) standard-of-care treatment options.\n   2. or for whom no effective standard treatment is available.\n   3. and whose disease has progressed or is refractory. Exceptional circumstances may apply as described in the protocol.\n2. Diagnosis of a rare cancer harbouring an actionable genomic alteration, or common cancer types with rare actionable genomic alterations, that has been identified using a validated next-generation sequencing method and for which there is a relevant open treatment arm within the DETERMINE trial.\n3. Life expectancy of at least three months.\n4. Patients are able to provide written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up. For patients under 16 years old, the parent or legal guardian will be asked to provide written informed consent and the patient will be asked to provide age-appropriate assent (written or verbal, commensurate with age and level of understanding).\n5. Patients with objectively evaluable or measurable disease, according to an assessment method appropriate for their cancer type.\n6. Patients must provide a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow and\u002For trephine, lymph node or lump biopsy samples may be taken. For patients with haematological malignancies, a skin punch biopsy may also be taken.\n7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status 2 may be considered on an individual basis) (adults), Karnofsky score ≥50% (TYA) or Lansky Play scales ≥50% (\\\u003C12 years). Please see specific treatment arm appendices for any variations on this criterion and for definitions of adult and paediatric populations. Note: Paediatric patients: patients with Central Nervous System (CNS) tumours and a stable neurological deficit may be eligible with a performance status below 50%, at the discretion of the Investigator. In such cases, the deficit must be stable for at least 7 days prior to trial enrolment and be assessed by the local investigator as due to tumour or due to a post-surgical AE.\n8. Women of childbearing potential are eligible provided that they meet the following criteria:\n\n   * Have a negative serum or urine pregnancy test before enrolment and\n   * Agree to the birth control methods and duration of use of those methods, as specified in each treatment arm appendix.\n9. Male patients with partners of childbearing potential are eligible provided that they agree to the birth control methods and duration of use of those methods, as specified in each treatment arm appendix.\n\nCore exclusion criteria:\n\n1. Ongoing AEs Common Terminology Criteria of Adverse Events (CTCAE) Grade ≥2 attributable to previous anti-cancer treatments. Exceptions to this are any clinically stable AEs, which in the opinion of the Investigator should not exclude the patient.\n2. At high medical risk, in the opinion of the Investigator, because of non-malignant systemic disease (including active uncontrolled infection).\n3. Female patients who are pregnant, breastfeeding or planning to become pregnant or male patients with a partner who is a woman of childbearing potential and is planning to become pregnant during the trial or following the last dose of IMP, as specified in each treatment arm appendix.\n4. Is (or plans to be) a patient in another interventional clinical trial, whilst taking part in this trial. Participation in an observational trial which does not involve administration of an Investigational Medicinal Product (IMP) and which, in the opinion of the local Investigator, would not place an unacceptable burden on the patient would be acceptable e.g. sample collection\\* or QoL studies.\n\n   \\*for paediatric patients participating in other studies involving tissue\u002Fcirculating tumour (ct) DNA\u002Fother blood collection, consideration would need to be given to the total blood volumes collected (as per the European Medicines Agency blood volume limits for children).\n5. Co-administration of anti-cancer therapies other than those administered in this trial (with the exception of lifelong hormone suppression such as luteinising hormone agonists\u002Fanalogues in prostate cancer).\n6. Radiotherapy (except for palliative reasons) or chemotherapy, endocrine therapy (except when given for conditions other than malignant disease; e.g. thyroid replacement for hypothyroidism, hydrocortisone for cortisol deficiency\u002Fpanhypopituitarism), nitrosoureas, mitomycin-C, immunotherapy and molecularly targeted agents or other IMPs within 4 weeks or 5 half-lives (whichever is the shorter).\n7. Rapidly progressing or symptomatically deteriorating brain metastases. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within the 14 days (for adult patients) or 7 days (for paediatric patients) prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or CNS malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and\u002For stereotactic radiosurgery at least 14 days prior to the start of IMP administration.\n8. Any other condition which, in the opinion of the local Investigator, would not be in the best interests of the patient.","ALL",{"count":19,"type":20},825,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE2","PHASE3","DETERMINE is an open-label phase II\u002FIII trial. It will look at targeted treatments in rare cancers or common cancers with rare genetic change (mutation). Patients must have a cancer with an identified mutation. This could be found during routine testing or as part of another research programme. The DETERMINE trial will recruit adults, teenagers and children. If a drug is found to benefit a new patient group, the study team will work with the NHS and the Cancer Drugs Funds to see if these drugs can be available for patients in the future. This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), additional records will be added to clinicaltrials.gov for each treatment arm.",[27,28],"Haematological Malignancy","Solid Tumour",[30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66],"Adult","Alectinib","ALK Tyrosine Kinase Receptor","Antineoplastic Agents","Atezolizumab","BRAF Kinase","Cancer","Child","CMMRD","Cobimetinib","Entrectinib","Genes, HER2","Immune Checkpoint Inhibitors","Immunological","Lymphoproliferative Disorders","Malignancy","Malignant Neoplasms","MSI","Molecular Targeted Therapy","Mutation","Neoplasms by Histologic Type","Neoplasms by Site","Paediatric","Pertuzumab","Precision Medicine","Protein Kinase Inhibitors","Rare","ROS1 protein, human","TMB","Trastuzumab","Tumour-agnostic","Vemurafenib","Young adult","Capmatinib","MET","Dabrafenib","Trametinib","RECRUITING","2026-06-29",{"date":70,"type":71},"2026-07-01","ACTUAL",{"date":73,"type":71},"2023-03-01",{"date":75,"type":20},"2029-10",{"name":77,"class":78},"Cancer Research UK","OTHER",27,{"id":81,"slug":82,"hasResults":11,"nctId":83,"briefTitle":84,"officialTitle":85,"acronym":4,"eligibilityCriteria":86,"healthyVolunteers":11,"sex":17,"minAge":87,"maxAge":4,"enrollmentInfo":88,"targetDuration":4,"studyType":21,"phases":90,"briefSummary":92,"conditions":93,"keywords":105,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":108,"lastUpdatePostDateStruct":109,"startDateStruct":111,"completionDateStruct":113,"leadSponsor":115,"locationsCount":116},"100545354","phase-1-a-phase-iii-trial-of-ucb4594-in-participants-with-advanced-cancer-100545354","NCT06380816","A Phase I\u002FII Trial of UCB4594 in Participants With Advanced Cancer","A Cancer Research UK Phase I\u002FII Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of UCB4594 Alone and in Combination With Anti-cancer Treatments in Participants With Advanced Malignancies","Inclusion Criteria:\n\n1. Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product (IMP) administration and follow-up\n2. Participant population: Histologically or cytologically proven advanced solid tumours (as specified below), refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the participant. Module A (dose escalation): Tumour types which have shown high levels of human HLA-G expression (as reported in the literature): head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer, triple-negative breast cancer, renal cell cancer (clear cell only), oesophago-gastric cancer (excluding gastrointestinal stromal tumour), cervical cancer, ovarian cancer, pancreatic cancer. N.B. Participants with small cell type cancers on histology\u002Fcytology are excluded. Pre-treatment biopsies are mandatory for all participants. Paired biopsies will be mandatory for participants from doses of 30 mg and higher. Participants must have disease amenable to biopsy (excluding bone metastases) as deemed safe by the Investigator\n3. Measurable disease, according to RECIST v1.1\n4. Life expectancy of at least 12 weeks\n5. Eastern Cooperative Oncology Group performance status of 0 or 1\n6. Haematological and biochemical indices within defined ranges. These measurements should be performed to confirm the patient's eligibility to participate in the trial\n7. Aged 18 years or over at the time consent is given. Participants aged 16-17 years may be eligible for recruitment to the backfill cohorts in dose escalation once adequate safety and toxicity data have been established in participants aged 18 years or over. All relevant data will be reviewed and a decision on the inclusion of participants aged 16-17 years will be made by the Trial Management Group\n\nExclusion Criteria:\n\n1. Radiotherapy (except palliative), endocrine therapy (unless for non-malignant disease), chemotherapy, targeted therapy or immunotherapy, or any other IMPs during the previous 4 weeks or 5 half-lives (whichever is shorter) before the first dose of IMP\n2. Ongoing toxicity of previous treatments \\>CTCAE Grade 1 (except alopecia of any grade, stable Grade 2 peripheral neuropathy or hormone-replacement therapy (HRT)-managed endocrine disorders)\n3. Patients with rapidly progressing \u002F symptomatically deteriorating brain\u002Fleptomeningeal metastases\u002Funtreated brain metastases are excluded. Patients with previously treated brain metastases are eligible if they haven't had a seizure or a clinically significant change in neurological status or required steroids in the last 2 weeks\n4. Pregnant or breastfeeding female patients (or planning to breastfeed)\n5. Women of childbearing potential. However, those not already pregnant or breastfeeding (or who discontinue breastfeeding) and meet the following are eligible:\n\n   5.1. Have a negative serum pregnancy test within 7 days before enrolment and either:\n\n   5.2.1. Agree to a form of highly effective contraception plus a barrier method, or\n\n   5.2.2. Agree to sexual abstinence\n\n   Effective from the negative pregnancy test, throughout the trial and for 10 months after the last dose of UCB4594\n6. Male patients with partners of childbearing potential. However, patients who meet the following are eligible:\n\n   6.1. Agree to a barrier method of contraception or sexual abstinence\n\n   6.2. Males with pregnant or breastfeeding partners must use barrier method contraception to prevent exposure of the foetus or neonate\n\n   6.3. Non-vasectomised males must also ensure any partner of childbearing potential uses highly effective contraception or agrees to sexual abstinence\n\n   Effective from the date of the first dose of UCB4594, throughout the trial and for 5 months after the last dose of UCB4594 N.B. Males must refrain from donating sperm for the same period\n7. Surgery from which the patient has not yet recovered\n8. High medical risk because of non-malignant systemic disease, including serious or uncontrolled infection (requiring intravenous antibiotics) or unexplained fever \\>38°C within 2 weeks prior to the first dose of UCB4594\n9. Known to be serologically positive for hepatitis B virus, hepatitis C virus or human immunodeficiency virus\n10. Active or suspected autoimmune disease, or any history of autoimmune condition that required systemic corticosteroids or immunosuppressive agents. Patients who have ever had a transplant are excluded. This does not apply to patients with: vitiligo, alopecia, or type I diabetes mellitus, psoriasis not requiring chronic systemic immunosuppressive treatment within the past 2 years, stable autoimmune-mediated hypothyroidism on HRT, and Raynaud's syndrome\n11. Are being treated with escalating or supraphysiologic doses of corticosteroids or immunosuppressive agents. Participants with immunotherapy-related hypophysitis adequately treated with physiologic doses of steroids are not excluded. Use of topical, ophthalmic, inhaled, intermittent steroid injections, and intranasal corticosteroids are permitted\n12. Hypersensitivity to the ingredients\u002Fexcipients (including polysorbate 80) in UCB4594\n13. History of significant toxicities from treatment of immune checkpoint inhibitors (CPIs) that necessitated permanent discontinuation (Patients who started on combination CPI \\[e.g., ipilimumab\u002Fnivolumab\\] and had toxicity requiring discontinuation of one CPI \\[e.g., continued with nivolumab single agent\\] are not excluded)\n14. History of Grade ≥3 infusion-related reaction to monoclonal antibodies or similar drugs\n15. Prior treatment with HLA-G, immunoglobulin-like transcript (ILT)2 or ILT4-targeting drug\n16. Live, attenuated vaccine within 28 days prior to the first dose of IMP\n17. Increased risk due to tumour flare (e.g., an initial increase in tumour size that may lead to obstruction of airways, etc)\n18. Significant active pulmonary disease or condition at screening, including:\n\n    18.1. Lymphangitis carcinomatosa\n\n    18.2. History of interstitial lung disease or pulmonary fibrosis\n\n    18.3. History of pulmonary inflammatory disease\n19. Evidence of bleeding diathesis\n20. Significant cardiovascular disease, defined as a history of: congestive heart failure requiring therapy or left ventricular ejection fraction \\\u003C40%, unstable angina pectoris or myocardial infarction within 6 months prior to entry, or current poorly controlled angina (symptoms weekly or more), clinically significant cardiac arrhythmia within 6 months prior to entry (asymptomatic atrial fibrillation or asymptomatic first-degree heart block permitted), or myocarditis. Presence of symptomatic or severe valvular heart disease. Baseline QT interval corrected by Fridericia \\>450 msec for males and \\>470 msec for females on triplicate electrocardiogram is ineligible\n21. Participant in or plans to join another interventional trial\n22. Other current malignancies. Cancer survivors who have undergone potentially curative therapy for prior malignancy with no evidence of disease for 3+ years are eligible\n23. Any other condition that, in the Investigator's opinion, means the trial is not in the patient's best interest","18 Years",{"count":89,"type":20},167,[91,23],"PHASE1","This clinical trial is looking at UCB4594. This is the first time the drug is being tested in humans. UCB4594 is a type of drug called a monoclonal antibody. It has been designed to work by targeting a protein called human leucocyte antigen G (HLA-G) that is found in high levels on some cancer cells. By attaching itself to this protein it may help the immune system to attack and kill the cancer cells.\n\nThe four main aims of the clinical trial are to find out:\n\n1. The best dose of UCB4594 that can be given safely to participants in the trial.\n2. What the side effects of UCB4594 are and how they can be managed.\n3. What happens to UCB4594 inside the body and how it affects cancer cells.\n4. Whether UCB4594 can cause cancer to shrink.",[94,95,96,97,98,99,100,101,102,103,104],"Advanced Solid Tumours","Squamous Cell Carcinoma of Head and Neck","Carcinoma, Non-Small-Cell Lung","Colorectal Neoplasms","Triple Negative Breast Neoplasms","Carcinoma, Renal Cell (Clear Cell Only)","Esophageal Neoplasms","Stomach Neoplasms (Excluding Gastrointestinal Stromal Tumors)","Uterine Cervical Neoplasms","Ovarian Neoplasms","Pancreatic Neoplasms",[106,107,36],"HLA-G","Monoclonal Antibody","2026-05-05",{"date":110,"type":71},"2026-05-08",{"date":112,"type":71},"2024-07-09",{"date":114,"type":20},"2029-11",{"name":77,"class":78},4,{"id":118,"slug":119,"hasResults":11,"nctId":120,"briefTitle":121,"officialTitle":122,"acronym":15,"eligibilityCriteria":123,"healthyVolunteers":11,"sex":17,"minAge":124,"maxAge":4,"enrollmentInfo":125,"targetDuration":4,"studyType":21,"phases":127,"briefSummary":128,"conditions":129,"keywords":141,"overallStatus":145,"whyStopped":4,"lastUpdateSubmitDate":146,"lastUpdatePostDateStruct":147,"startDateStruct":149,"completionDateStruct":151,"leadSponsor":152,"locationsCount":79},"100626796","phase-2-determine-trial-treatment-arm-07-dabrafenib-in-combination-with-trametinib-in-adult-paediatric-and-teenageyoung-adult-patients-with-braf-v600-mutation-positive-cancers-100626796","NCT07440290","DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With BRAF V600 Mutation-Positive Cancers.","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and TYA Patients With BRAF V600 Mutation-Positive Cancers.","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 07 (DABRAFENIB AND TRAMETINIB) OUTLINED BELOW\\* \\*When dabrafenib- and trametinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the dabrafenib- and trametinib-specific criteria will take precedence.\n\nInclusion criteria:\n\nA. Confirmed diagnosis of a malignancy harbouring an oncogenic alteration in BRAF V600, including Langerhans cell histiocytosis, using an analytically validated next-generation sequencing method.\n\nB. Patients ≥1 year old and ≥8 kg in body weight.\n\nC. Women of childbearing potential are eligible provided that they meet the following criteria:\n\n• Have a negative serum or urine pregnancy test before enrolment and;\n\n• Agree to use one form of a non-hormonal highly effective contraception method (a method that can achieve a failure rate of \\\u003C1% when used consistently and correctly; the requirement for non-hormonal method is because dabrafenib may decrease the efficacy of oral or any systemic hormonal contraceptives), such as: i. intrauterine device (IUD), ii. bilateral tubal occlusion, bilateral tubal ligation (at least six weeks before taking trial treatment), iii. vasectomised partner, iv. total sexual abstinence. Effective from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).\n\nPatients who are breastfeeding must be willing to discontinue breastfeeding from the start of treatment, throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).\n\nD. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks after the last administration of dabrafenib and 16 weeks after the last administration of trametinib (whichever is later):\n\n* Agree to take measures not to father children by using a barrier method of contraception (male condom plus spermicide) or to sexual abstinence.\n* Non-vasectomised male partners with partners who are women of childbearing potential should also be advised of the benefit for their partner of using a highly effective method of contraception, such as:\n\n  i. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \\[oral, intravaginal or transdermal\\]), ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), iii. IUD, iv. intrauterine hormone-releasing system (IUS), v. bilateral tubal occlusion, vi. total sexual abstinence.\n* Male patients with pregnant or breastfeeding partners must be advised to use barrier method contraception (male condom) to prevent drug exposure of the foetus or neonate, even if vasectomised.\n* Male patients must refrain from donating sperm for the same period.\n\nE. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nF. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility\n\nExclusion criteria:\n\nA. Diagnosis of one of the following BRAF V600E mutation-positive cancers:\n\n* Colorectal cancer in adult (≥18 years) patients;\n* Unresectable or metastatic melanoma in adult (≥18 years) patients;\n* Advanced non-small cell lung cancer in adult (≥18 years) patients;\n* Gliomas harbouring a BRAF V600E mutation in paediatric (1 to \\\u003C16 years) or TYA (16 to \\\u003C18 years) patients.\n\nB. Previous treatment with dabrafenib and trametinib in combination (or other BRAF and MEK inhibitors in combination) for the current indication.\n\nC. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for two weeks following their last dose of dabrafenib or 16 weeks following their last dose of trametinib, whichever is later.\n\nD. Known hypersensitivity to dabrafenib or trametinib or any of the excipients. See the current relevant SmPCs (UK) for the full lists.\n\nE. Patients with a history of retinal vein occlusion.\n\nF. Any impairment of gastrointestinal (GI) function of uncontrolled GI disease that may significantly alter the administration or absorption of dabrafenib and\u002For trametinib (e.g. history of diverticulitis, metastases to the GI tract, uncontrolled Crohn's disease, uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome or short gut syndrome).\n\nG. Clinically significant cardiac or cerebrovascular disease as defined by:\n\n* Unstable angina within three months prior to screening;\n* Myocardial infarction within three months prior to screening;\n* History of documented congestive heart failure (New York Heart Association functional classification III\u002FIV) etc.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attack \\[TIA\\]) within three months prior to screening.\n\n• Patients with primary central nervous system (CNS) tumours may be considered unless intratumoural bleeding has occurred within two weeks prior to the first dose of dabrafenib and trametinib, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nH. Patients who were administered a live, attenuated vaccine within 28 days prior to initiation of treatment, or anticipation of need for such a vaccine during investigational medicinal product (IMP) treatment or within six months after the final dose of dabrafenib and trametinib.\n\nI. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of dabrafenib and trametinib including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided that each of the following conditions are met:\n\n* CD4 count ≥350\u002FµL;\n* Undetectable viral load;\n* Receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* No HIV\u002Facquired immune deficiency syndrome associated opportunistic infection in the last 12 months.\n\nJ. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial (including absorption of oral medications) that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.","1 Year",{"count":126,"type":20},30,[23,24],"This clinical trial is looking at two drugs called dabrafenib and trametinib. Dabrafenib and trametinib are approved as standard of care treatment for adult patients with melanoma (a type of skin cancer) or lung cancer and in children with glioma (a type of brain tumour). This means they have gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Dabrafenib and trametinib work in patients with a particular mutation in their cancer known as BRAF V600.\n\nInvestigators now wish to find out if they will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[27,130,44,50,51,131,132,133,36,134,135,103,97,136,137,138,139,140,28],"Malignant Neoplasm","Gastrointestinal Cancer","Non-Melanoma Skin Cancer (NMSC)","Langerhans Cell Histiocytosis (LCH)","Erdheim-Chester Disease","Thyroid Carcinoma, Papillary","Laryngeal Neoplasms","Carcinoma, Non-Small Cell-Lung","Glioma","Multiple Myeloma","Thyroid Carcinoma, Anaplastic",[30,33,36,37,65,45,46,48,49,142,51,52,54,143,55,56,66,144,62],"Neoplasms by Histologic Site","Proto-Oncogene Proteins B-raf","Tumour-Agnostic","NOT_YET_RECRUITING","2026-02-23",{"date":148,"type":71},"2026-02-27",{"date":150,"type":20},"2026-02",{"date":75,"type":20},{"name":77,"class":78},{"id":154,"slug":155,"hasResults":11,"nctId":156,"briefTitle":157,"officialTitle":158,"acronym":15,"eligibilityCriteria":159,"healthyVolunteers":11,"sex":17,"minAge":160,"maxAge":4,"enrollmentInfo":161,"targetDuration":4,"studyType":21,"phases":162,"briefSummary":163,"conditions":164,"keywords":172,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":176,"lastUpdatePostDateStruct":177,"startDateStruct":179,"completionDateStruct":181,"leadSponsor":182,"locationsCount":79},"100499704","phase-2-determine-trial-treatment-arm-04-trastuzumab-in-combination-with-pertuzumab-in-adult-paediatric-and-teenageyoung-adult-patients-with-cancers-with-her2-amplification-or-activating-mutations-100499704","NCT05786716","DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage\u002FYoung Adult Patients With Cancers With HER2 Amplification or Activating Mutations","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage\u002FYoung Adult Patients With Cancers With HER2 Amplification or Activating Mutations.","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 04 (TRASTUZUMAB AND PERTUZUMAB) OUTLINED BELOW\\*\n\n\\*When trastuzumab- and pertuzumab-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the trastuzumab- and pertuzumab-specific criteria will take precedence.\n\nInclusion Criteria:\n\nA. Confirmed diagnosis of a malignancy harbouring HER2 amplification, or an appropriate activating mutation as defined by the MTB, using an analytically validated next-generation sequencing method.\n\n• A HER2 amplification copy number between 5-9 will require an MTB discussion. A HER2 amplification copy number ≥10 will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities (such as multiple gene amplifications) that require MTB discussion.\n\nB. Age 12 years or above.\n\nC. Women of childbearing potential are eligible provided that they meet the following criteria:\n\nHave a negative serum or urine pregnancy test before enrolment and;\n\nAgree to use one form of effective birth control method such as:\n\nI. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal):\n\nII. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable)\n\nIII. intrauterine device (IUD)\n\nIV. intrauterine hormone-releasing system (IUS)\n\nV. bilateral tubal occlusion\n\nVI. vasectomised partner\n\nVII. sexual abstinence\n\nVIII. male or female condom with or without spermicide\n\nIX. cap, diaphragm or sponge with spermicide\n\nEffective from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later).\n\nD. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later):\n\n* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence.\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception as in C, above.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nE. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nF. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nG. PAEDIATRIC PATIENTS (\\\u003C18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nExclusion Criteria:\n\nA. Diagnosis of HER2-positive early or metastatic breast cancer.\n\nB. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within seven months following their last dose of trastuzumab or pertuzumab (whichever is later).\n\nC. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.\n\nD. Known hypersensitivity to trastuzumab or pertuzumab, murine proteins, or to any of the excipients.\n\nE. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during trastuzumab and pertuzumab treatment or within six months after the final dose of trastuzumab and pertuzumab.\n\nF. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias (within three months), NYHA class III or IV congestive heart failure.\n\nLeft Ventricular Ejection Fraction \\\u003C55%.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attack \\[TIA\\]) or cardiovascular event (including acute myocardial infarction \\[MI\\]) within three months before the first dose of trastuzumab and pertuzumab.\n\n• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of trastuzumab and pertuzumab, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nG. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to trastuzumab or pertuzumab.\n\nH. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.\n\nI. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of trastuzumab and pertuzumab, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:\n\n* CD4 count ≥350\u002FμL;\n* undetectable viral load;\n* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* no HIV\u002F acquired immune deficiency syndrome (AIDS)-associated opportunistic infection in the last 12 months.","12 Years",{"count":126,"type":20},[23,24],"This clinical trial is looking at a combination of drugs called trastuzumab and pertuzumab. This combination of drugs is approved together as standard of care treatment for adult patients with breast cancer (often with other anti-cancer drugs). This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.\n\nTrastuzumab and pertuzumab work in patients with these types of cancers which have a molecular alteration called HER2 amplification or HER2 activating mutation.\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which are also HER2 amplified or HER2 mutated. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[27,97,165,166,167,168,169,103,170,171,28],"Urinary Bladder Neoplasm","Gallbladder Neoplasms","Salivary Gland Neoplasm","Lung Neoplasm","Pancreatic Neoplasm","Prostatic Neoplasm","Skin Neoplasm",[30,173,36,37,48,49,52,53,54,56,174,175,59,60,62],"Antibodies, monoclonal","Receptor, ErbB-2","Targeted","2025-11-25",{"date":178,"type":71},"2025-12-02",{"date":180,"type":71},"2023-03-07",{"date":75,"type":20},{"name":77,"class":78},{"id":184,"slug":185,"hasResults":11,"nctId":186,"briefTitle":187,"officialTitle":188,"acronym":15,"eligibilityCriteria":189,"healthyVolunteers":11,"sex":17,"minAge":87,"maxAge":4,"enrollmentInfo":190,"targetDuration":4,"studyType":21,"phases":191,"briefSummary":192,"conditions":193,"keywords":197,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":210,"startDateStruct":212,"completionDateStruct":214,"leadSponsor":215,"locationsCount":216},"100592057","phase-2-determine-trial-treatment-arm-06-capmatinib-in-adult-patients-with-cancers-harbouring-met-dysregulations-100592057","NCT06988475","DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 06 (CAPMATINIB) OUTLINED BELOW\\*\n\n\\*When capmatinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the capmatinib-specific criteria will take precedence.\n\nInclusion criteria:\n\nA. Confirmed diagnosis of a MET-positive malignancy using an analytically next-generation sequencing method (METex14 skipping, MET amplification, MET fusion, or MET activating mutation).\n\nB. Adult patients ≥18 years old.\n\nC. Women of childbearing potential are eligible, provided that they meet the following criteria:\n\n* Have a negative serum or urine pregnancy test before enrolment, and\n* Agree to use one form of highly effective birth control method (a method that can achieve a failure rate of \\\u003C1% when used consistently and correctly), such as:\n\nI. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \\[oral, intravaginal or transdermal\\])\n\nII. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)\n\nIII. intrauterine device (IUD)\n\nIV. Intrauterine hormone-releasing system (IUS)\n\nV. bilateral tubal occlusion\n\nVI. vasectomised partner\n\nVII. sexual abstinence\n\nEffective from the first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib.\n\nD. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib:\n\n* Agree to take measures not to father children by using a barrier method of contraception (e.g. condom) or sexual abstinence.\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception, as in criterion C above.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nE. Patients must be able and willing to undergo a fresh biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nF. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nExclusion criteria:\n\nA. Diagnosis of NSCLC with METex14 skipping mutation or MET amplification.\n\nB. Prior treatment with a selective MET inhibitor or HGF-targeting therapy unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to capmatinib.\n\nC. Carcinomatous meningitis.\n\nD. Presence or history of additional malignant disease that has been diagnosed and\u002For required therapy within the past three years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.\n\nE. Presence or history of interstitial lung disease (ILD) and\u002For interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention) and evidence of active pneumonitis on screening chest computed tomography (CT) scan. Prior localised radiotherapy related pneumonitis is permitted if resolved and off steroids and asymptomatic for at least six months.\n\nF. Clinically significant, uncontrolled heart disease such as:\n\n* Unstable angina within three months prior to screening\n* Myocardial infarction within three months prior to screening\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\n* Uncontrolled hypertension defined by a systolic blood pressure ≥160 mm Hg and\u002For diastolic blood pressure ≥100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attack \\[TIA\\]) within three months before screening.\n\n• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within two weeks of the first dose of capmatinib, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nG. History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the trial such as:\n\n* Concomitant clinically significant cardiac arrhythmias (atrial and ventricular), e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker\n* History of familial long QT syndrome or known family history of Torsades de Pointes\n* Resting QTcF (Corrected QT interval by Fridericia formula) ≥450 msec (male) or ≥460 msec (female) at screening ECG (as a mean of triplicate ECG)\n\nH. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within four weeks prior to starting trial treatment (two weeks for resection of brain lesions) or patients who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the trial at least one week after the procedure.\n\nI. Patients receiving treatment with strong inducers of cytochrome P450 (CYP) 3A that cannot be discontinued at least one week prior to the start of treatment with capmatinib and for the duration of the trial.\n\nJ. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial (including absorption of oral medications) that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.\n\nK. Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the administration or absorption of capmatinib (e.g., Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome or short gut syndrome). Unable to swallow capmatinib intact, without chewing or crushing the tablets (as per the dosing schedule).\n\nL. Active infections including, but not limited to, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Screening for known chronic conditions is not required. Patients with known serological evidence of chronic HBV or HCV infection whose disease is controlled under antiviral therapy according to local regulation are eligible. Patients with history of testing positive for human immunodeficiency virus (HIV) infection are eligible provided the each of the following conditions are met:\n\n* CD4 count ≥350\u002FμL;\n* undetectable viral load;\n* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* no HIV\u002F acquired immune deficiency syndrome-associated opportunistic infection in the last 12 months.\n\nM. Known hypersensitivity to any of the excipients of capmatinib.\n\nN. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the two weeks prior to trial entry to manage CNS symptoms. Primary brain or CNS malignancies are allowed providing the patient is clinically stable (if corticosteroids are required, they must be at a stable or decreasing dose for at least 14 days prior to Cycle 1 Day 1). If patients are on corticosteroids for endocrine deficiencies or tumour-associated symptoms other than CNS related, the dose must have been stabilised (or decreasing) for at least five days before Cycle 1 Day 1.\n\nO. Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least one week before first dose of capmatinib, and for the duration of the trial. Patients on non-enzyme-inducing anticonvulsants are eligible.\n\nP. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for seven days following their last dose of capmatinib.\n\nQ. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during capmatinib treatment or within six months after the final dose of capmatinib.",{"count":126,"type":20},[23,24],"This clinical trial is looking at a drug called capmatinib. Capmatinib is approved as standard of care treatment for adult patients with certain types of lung cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.\n\nCapmatinib works in patients with lung cancer with a particular mutation in their cancer known as a METex14 skipping mutation.\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation or other specific mutations or changes which take place in the MET gene. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[28,27,130,50,51,36,45,138,194,195,196],"Neuroblastoma","Gastric Cancer","Soft Tissue Sarcoma",[198,199,200,201,202,203,204,205,33,206,207,46,48,49,50,51,54,55,56,60,208],"adult","capmatinib","MET Tyrosine Kinase Receptor","MET exon 14 skipping","MET amplifications","MET fusions","MET activating mutations","MET dysregulations","cancer","malignancy","METex14 skipping","2025-11-19",{"date":211,"type":71},"2025-11-24",{"date":213,"type":71},"2024-11-19",{"date":75,"type":20},{"name":77,"class":78},17,{"id":218,"slug":219,"hasResults":11,"nctId":220,"briefTitle":221,"officialTitle":222,"acronym":15,"eligibilityCriteria":223,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":224,"targetDuration":4,"studyType":21,"phases":225,"briefSummary":226,"conditions":227,"keywords":231,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":232,"startDateStruct":233,"completionDateStruct":235,"leadSponsor":236,"locationsCount":79},"100498421","phase-2-determine-trial-treatment-arm-01-alectinib-in-adult-paediatric-and-teenageyoung-adult-patients-with-alk-positive-cancers-100498421","NCT05770037","DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With ALK Positive Cancers","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With ALK Positive Cancers","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 01 (ALECTINIB) OUTLINED BELOW\\*\n\n\\*When alectinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the alectinib-specific criteria will take precedence.\n\nInclusion Criteria:\n\nA. Confirmed diagnosis of an ALK-positive malignancy using an analytically validated next-generation sequencing method.\n\nB. Women of childbearing potential are eligible, provided that they meet the following criteria:\n\n* Have a negative serum or urine pregnancy test before enrolment and;\n* Agree to use one form of highly effective birth control method such as:\n\nI. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \\[oral, intravaginal or transdermal\\]\n\nII. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)\n\nIII. intrauterine device (IUD)\n\nIV. intrauterine hormone-releasing system (IUS)\n\nV. bilateral tubal occlusion\n\nVI. vasectomised partner\n\nVII. sexual abstinence\n\nEffective from the first administration of alectinib, throughout the trial and for three months after the last administration of alectinib.\n\nC. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of alectinib, throughout the trial and for three months after the last administration of alectinib:\n\n* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence.\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception, as in criterion B, above.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nD. Patients must be able and willing to undergo a fresh tissue biopsy. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nE. Paediatric patients (patients aged \\\u003C18 years) must have a body weight ≥40kg.\n\nF. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nG. PAEDIATRIC PATIENTS (\\\u003C18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.\n\nExclusion Criteria:\n\nA. Diagnosis of ALK-positive non-small cell lung cancer.\n\nB. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for three months following their last dose of alectinib.\n\nC. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to alectinib. Patients who have previously received crizotinib (Xalkori\\^\\[®\\]) and did not respond, or who responded inadequately or responded adequately and subsequently progressed, are allowed into the trial.\n\nD. History of or radiological evidence of interstitial lung disease and\u002For pneumonitis. Prior localised radiotherapy related pneumonitis is permitted if resolved and off steroids and asymptomatic for \\>6 months.\n\nE. Patients at risk of gastrointestinal (GI) perforation e.g. history of diverticulitis, concomitant use of medicinal product with a recognized risk of GI perforation (unless patient has also been co-prescribed gastric protection).\n\n• Patients who present with a GI primary tumour or metastases to the GI tract may be considered.\n\nF. Patient unable to swallow or tolerate oral medication or any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or following major bowel resection. Paediatric patients will be excluded if they are unable to swallow the capsules, as per the dosing schedule (150 mg dose strength).\n\nG. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias (within three months), or New York Heart Association (NYHA) class III or IV congestive heart failure.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attack \\[TIA\\]), or cardiovascular event (including acute myocardial infarction \\[MI\\]), within three months before the first dose of alectinib.\n\n• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of alectinib, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nH. History of organ transplantation.\n\nI. Symptomatic bradycardia for age.\n\nJ. Known hypersensitivity to alectinib or any of the excipients. See the current alectinib (Alecensa® 150 mg hard capsules) SmPC for the full list.\n\nK. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during alectinib treatment or within six months after the final dose of alectinib.\n\nL. Active hepatitis B or C virus or known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS) related illness. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:\n\n* CD4 count ≥350\u002FμL;\n* undetectable viral load;\n* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* no HIV\u002FAIDS-associated opportunistic infection in the last 12 months.\n\nM. Familial or personal history of congenital bone disorders, bone metabolism alterations or known osteopenia in the patient.\n\nN. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.",{"count":126,"type":20},[23,24],"This clinical trial is looking at a drug called alectinib. Alectinib is approved as standard of care treatment for adult patients with certain types of lung cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Alectinib works in lung cancer patients with a particular mutation in their cancer known as ALK.\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[27,130,44,50,51,36,228,229,230,194,28],"Anaplastic Large Cell Lymphoma","Lymphoma","Renal Cell Carcinoma",[30,31,32,33,36,37,45,46,48,49,142,51,52,54,55,56,60,62],{"date":211,"type":71},{"date":234,"type":71},"2023-12-18",{"date":75,"type":20},{"name":77,"class":78},{"id":238,"slug":239,"hasResults":11,"nctId":240,"briefTitle":241,"officialTitle":242,"acronym":15,"eligibilityCriteria":243,"healthyVolunteers":11,"sex":17,"minAge":87,"maxAge":4,"enrollmentInfo":244,"targetDuration":4,"studyType":21,"phases":245,"briefSummary":246,"conditions":247,"keywords":250,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":251,"startDateStruct":252,"completionDateStruct":253,"leadSponsor":254,"locationsCount":255},"100498278","phase-2-determine-trial-treatment-arm-05-vemurafenib-in-combination-with-cobimetinib-in-adult-patients-with-braf-positive-cancers-100498278","NCT05768178","DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 05 (VEMURAFENIB AND COBIMETINIB) OUTLINED BELOW\\*\n\n\\*When vemurafenib and cobimetinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the vemurafenib and cobimetinib-specific criteria will take precedence.\n\nInclusion Criteria:\n\nA. Confirmed diagnosis of a malignancy harbouring any actionable BRAF V600 mutation using an analytically validated next-generation sequencing method.\n\nB. Adult patients ≥18 years old.\n\nC. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nD. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nE. Women of childbearing potential are eligible provided that they meet the following criteria:\n\n* Have a negative serum or urine pregnancy test before enrolment and;\n* Agree to sexual abstinence OR to use any two forms of highly effective or effective methods together (at least one to be non-hormonal) such as:\n\n  * Highly effective methods:\n* combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)\n* progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)\n* intrauterine device (IUD)\n* intrauterine hormone-releasing system (IUS)\n* bilateral tubal occlusion\n* vasectomised partner\n\n  * Effective methods:\n* progestogen-only oral hormonal contraception not associated with inhibition of ovulation\n* male or female condom with or without spermicide\n* cap, diaphragm or sponge with spermicide\n\nEffective from the first administration of vemurafenib or cobimetinib (whichever is first), throughout the trial and for six months after the last administration of vemurafenib or cobimetinib (whichever is later).\n\nF. Male patients with partners who are women of childbearing potential, are eligible provided that they agree to the following, from the first administration of vemurafenib or cobimetinib (whichever is first), throughout the trial and for six months after the last administration of vemurafenib or cobimetinib (whichever is later):\n\n* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception as in E, above.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nExclusion Criteria:\n\nA. Diagnosis of unresectable or metastatic melanoma with a BRAF V600 mutation.\n\nB. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for six months following their last dose of vemurafenib or cobimetinib, whichever is later.\n\nC. Patients with QTcF (Corrected QT interval by Fridericia) at screening of \\>450 ms for males and \\>470 ms for females measured on triplicate ECG (if 1\u002F3 readings show \\>450\u002F470 ms then patient is ineligible).\n\nD. Patients with any history of long QT syndrome or Torsades de Pointes (or any concurrent medication with a known risk of inducing Torsades de Pointes).\n\nE. Known hypersensitivity to vemurafenib or cobimetinib or any of the excipients.\n\nF. Patients unable to swallow vemurafenib and cobimetinib intact, without chewing or crushing the tablets (as per the dosing schedule).\n\nG. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during vemurafenib and cobimetinib treatment or within six months after the final dose of vemurafenib and cobimetinib.\n\nH. Patients with clinically significant pre-existing cardiac conditions including (within the last three months prior to screening):\n\n* Uncontrolled or symptomatic angina,\n* Uncontrolled atrial or ventricular arrhythmias,\n* Class III \\& IV New York Heart Association congestive heart failure,\n* Left ventricular ejection fraction (LVEF) \\\u003C50%,\n* Myocardial infarction\n\nI. Ophthalmological disorders: History of retinal detachment, severe visual impairment, central serous chorioretinopathy, neovascular retinopathy, or retinopathy of prematurity.\n\nPatients with low grade gliomas causing visual impairment may be considered eligible and monitored with close ophthalmological monitoring.\n\nJ. History of pancreatitis.\n\nK. History of central nervous system (CNS) or gastrointestinal (GI) haemorrhage within three months of trial entry.\n\nL. Patients with any history of haemorrhagic stroke.\n\nM. Prior treatment with the same class of drug unless presence of a resistance alteration known to be potentially sensitive to either vemurafenib or cobimetinib. Prior sorafenib use is permissible following a washout period of 10 days.\n\nN. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.\n\nO. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of vemurafenib and cobimetinib, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:\n\n* CD4 count ≥350\u002FμL;\n* undetectable viral load;\n* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* no HIV\u002F acquired immune deficiency syndrome-associated opportunistic infection in the last 12 months.",{"count":126,"type":20},[23,24],"This clinical trial is looking at a combination of drugs called vemurafenib and cobimetinib. Vemurafenib is approved as standard of care for adult patients with unresectable or metastatic melanoma. Cobimetinib is approved as standard of care in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.\n\nCobimetinib and vemurafenib work in patients with these types of cancers which have certain changes in the cancer cells called BRAF V600 mutation-positive.\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which are also BRAF V600 mutation-positive. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[27,248,249,103,97,136,96,138,139,134,140,28],"Melanoma","Thyroid Cancer, Papillary",[30,33,36,45,46,48,49,50,51,54,39,143,56,60,61],{"date":211,"type":71},{"date":73,"type":71},{"date":75,"type":20},{"name":77,"class":78},16,{"id":257,"slug":258,"hasResults":11,"nctId":259,"briefTitle":260,"officialTitle":261,"acronym":15,"eligibilityCriteria":262,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":263,"targetDuration":4,"studyType":21,"phases":264,"briefSummary":265,"conditions":266,"keywords":268,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":271,"startDateStruct":272,"completionDateStruct":274,"leadSponsor":275,"locationsCount":79},"100498460","phase-2-determine-trial-treatment-arm-03-entrectinib-in-adult-paediatric-and-teenageyoung-adult-patients-with-ros1-gene-fusion-positive-cancers-100498460","NCT05770544","DETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With ROS1 Gene Fusion-Positive Cancers.","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With ROS1 Gene Fusion-Positive Cancers.","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 03 (ENTRECTINIB) OUTLINED BELOW\\*\n\n\\*When entrectinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the entrectinib-specific criteria will take precedence.\n\nInclusion Criteria:\n\nA. Confirmed diagnosis of a ROS1 gene fusion-positive malignancy, other than NSCLC, that has been identified using an analytically validated next-generation sequencing method.\n\nB. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nC. Patients with a BSA of 0.43m\\^2 and over.\n\nD. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nE. PAEDIATRIC PATIENTS (\\\u003C18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nF. Women of childbearing potential are eligible provided that they meet the following criteria:\n\n* Have a negative serum or urine pregnancy test before enrolment and either:\n* Agree to use one form of highly effective birth control method such as:\n\nI. Oral, intravaginal or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation\n\nII. Oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation\n\nIII. Intrauterine device (IUD)\n\nIV. Intrauterine hormone-releasing system (IUS)\n\nV. Bilateral tubal occlusion\n\nVI. Vasectomised partner\n\nPlus a barrier method if using a hormonal method: male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide OR\n\n• Sexual abstinence;\n\nEffective from the first administration of entrectinib, throughout the trial and for five weeks after the last administration of entrectinib.\n\nG. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of entrectinib, throughout the trial and for three months after the last administration of entrectinib:\n\n* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence.\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception as in F above.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nExclusion Criteria:\n\nA. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five weeks following their last dose of entrectinib\n\nB. Diagnosis of ROS1 fusion-positive NSCLC\n\nC. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to entrectinib\n\nD. Patients with significant cardiovascular disease are excluded as defined by:\n\ni. Current congestive heart failure requiring therapy (New York Heart Association III or IV) or known left ventricular ejection fraction (LVEF) \\\u003C50% (moderate to severe).\n\nii. History of unstable angina pectoris or myocardial infarction up to three months prior to trial entry, or current poorly controlled angina (symptoms weekly or more).\n\niii. Presence of symptomatic or severe valvular heart disease (severe by local echo graphic criteria or American Heart Association\u002FAmerican Cardiac College Stage C or D).\n\niv. History of a clinically significant cardiac arrhythmia up to three months prior to trial entry (asymptomatic atrial fibrillation or asymptomatic first-degree heart block are permitted.\n\nv. History of stroke (ischaemic or haemorrhagic) within the last three months.\n\n• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of entrectinib, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nE. Patients with a baseline QTcF (Corrected QT interval by Fridericia formula) interval longer than 450 milliseconds (ms) for male patients and 470 ms for female patients, patients with congenital long QTcF syndrome, and patients taking medicinal products that are known to prolong the QTc interval.\n\nF. History of additional risk factors for Torsades de Pointes (e.g., family history of long QT syndrome)\n\nG. Grade ≥2 peripheral neuropathy\n\nH. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of entrectinib, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:\n\n* CD4 count ≥350\u002FμL;\n* undetectable viral load;\n* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* no HIV\u002F acquired immune deficiency syndrome (AIDS)-associated opportunistic infection in the last 12 months.\n\nI. Known hypersensitivity to entrectinib or any of the excipients\n\nJ. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during entrectinib treatment or within six months after the final dose of entrectinib\n\nK. Patient unable to swallow entrectinib intact, without chewing, crushing or opening the capsules (as per the dosing schedule and suitable dosing strengths available). Any active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably affect drug absorption\n\nL. Patients with personal history of significant osteopenia (screening for osteopenia not required)\n\nM. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial",{"count":126,"type":20},[23,24],"This clinical trial is looking at a drug called entrectinib. Entrectinib is approved as standard of care treatment for adult patients with non-small cell lung cancer (NSCLC) which have a particular molecular alteration called ROS1-positive, and patients 12 years old or above with solid tumours which have another type of change in the cancer cells. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which have the same molecular alteration (ROS1-positive). If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[27,45,130,44,50,51,36,267,248,138,28],"Brain Neoplasms",[30,33,36,37,40,45,46,48,49,142,51,269,52,55,56,270,60,62],"Oncogene","ROS1 Protein, human",{"date":211,"type":71},{"date":273,"type":20},"2025-11-30",{"date":75,"type":20},{"name":77,"class":78},{"id":277,"slug":278,"hasResults":11,"nctId":279,"briefTitle":280,"officialTitle":281,"acronym":15,"eligibilityCriteria":282,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":283,"targetDuration":4,"studyType":21,"phases":284,"briefSummary":285,"conditions":286,"keywords":289,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":290,"startDateStruct":291,"completionDateStruct":293,"leadSponsor":294,"locationsCount":79},"100498426","phase-2-determine-trial-treatment-arm-02-atezolizumab-in-adult-paediatric-and-teenageyoung-adult-patients-with-cancers-with-high-tumour-mutational-burden-tmb-or-microsatellite-instability-high-msi-high-or-proven-constitutional-mismatch-repair-deficiency-cmmrd-disposition-100498426","NCT05770102","DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Paediatric and Teenage\u002FYoung Adult Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 02: Atezolizumab in Adult, Paediatric and Teenage\u002FYoung Adult Patients With Cancers With High TMB or MSI-high or Proven CMMRD Disposition.","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 02 (ATEZOLIZUMAB) OUTLINED BELOW\\*\n\n\\*When atezolizumab-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the atezolizumab-specific criteria will take precedence.\n\nInclusion Criteria:\n\nA. Confirmed diagnosis of a malignancy that is high TMB (defined as ≥10 mut\u002FMb), MSI-high or of proven (previously diagnosed) CMMRD disposition using an analytically validated next-generation sequencing method. Patient cases with TMB between 10-15 mut\u002FMb may be discussed in an MTB meeting. TMB ≥19 mut\u002FMb will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities (such as multiple gene amplifications) that require MTB discussion.\n\nB. Women of childbearing potential are eligible provide they meet the following criteria:\n\n* Have a negative serum or urine pregnancy test before enrolment and;\n* Agree to use one form of effective birth control method such as:\n\nI. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (\\[oral, intravaginal or transdermal\\]);\n\nII. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable);\n\nIII. intrauterine device (IUD),\n\nIV. intrauterine hormone-releasing system (IUS),\n\nV. bilateral tubal occlusion,\n\nVI. vasectomised partner,\n\nVII. sexual abstinence,\n\nVIII. male or female condom with or without spermicide;\n\nIX. cap, diaphragm or sponge with spermicide.\n\nEffective from the first administration of atezolizumab, throughout the trial and for five months after the last administration of atezolizumab.\n\nC. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of atezolizumab, throughout the trial until the last administration of atezolizumab:\n\n* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence.\n* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception.\n* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.\n\nAll male patients must refrain from donating sperm for the same period.\n\nD. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nE. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nF. PAEDIATRIC PATIENTS (\\\u003C18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.\n\nG. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted.\n\nExclusion Criteria:\n\nA. Diagnosis of urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma or triple negative breast cancer.\n\nB. Patients with rapidly progressing or symptomatically deteriorating brain metastases and\u002For leptomeningeal disease. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within 14 days (for adult patients) or 7 days (for paediatric patients) prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or central nervous system (CNS) malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and\u002For stereotactic radiosurgery at least 14 days prior to the start of IMP administration.\n\n• Paediatric patients with either primary brain tumours or extracranial solid tumours with intracranial metastases with one or more intracranial lesions should only be considered for inclusion if largest intracranial lesion is ≤6 cm in longest axis. Consideration should also be given to the intracranial location of the tumour and potential risk should swelling occur. This is because of the class risk of immune checkpoint inhibitors such as atezolizumab causing immune-mediated inflammatory response and 'tumour flare' which may result in acute neurological deterioration.\n\nC. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five months following their last dose of atezolizumab.\n\nD. History or clinical evidence of current inflammatory lung disease:\n\n* History of idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.\n* Evidence of active pneumonitis on screening chest computed tomography (CT) scan.\n\nE. Active autoimmune disease that requires the use of systemic immunomodulatory therapy (i.e. with disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy for hypothyroidism and adrenal or pituitary insufficiency is acceptable.\n\nF. Ongoing lung pathologies which, in the opinion of the Investigator present a compromise to safety (e.g. active tuberculosis).\n\nG. Systemic immunomodulatory agents within 14 days prior to trial entry (immunostimulatory agents within four weeks). Exceptions to this are:\n\n* Patients who received acute, low dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are eligible for the trial.\n* Patients who received corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma equivalent to ≤10 mg prednisolone a day or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial.\n* Patients with primary CNS disease can be receiving concurrent treatment with corticosteroids. Patients must be receiving a stable or decreasing dose for ≥14 days for adults and ≥7 days for paediatric patients prior to the screening magnetic resonance imaging (MRI) scan and at the time of drug initiation.\n* Patients who receive physiological doses of steroid replacement (e.g. hydrocortisone) are permitted.\n\nH. Known to be serologically positive (as detected by polymerase chain reaction) for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).\n\nI. History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins including other immune checkpoint inhibitors.\n\nJ. Known hypersensitivity to Chinese hamster ovary cell products.\n\nK. Known hypersensitivity to atezolizumab or any of the excipients.\n\nL. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during atezolizumab treatment or within six months after the final dose of atezolizumab.\n\nM. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or NYHA class III or IV congestive heart failure.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attacks \\[TIA\\]) or cardiovascular event (including acute myocardial infarction \\[MI\\]) within three months before the first dose of atezolizumab.\n\n• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of atezolizumab, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nPatients with a prior history of pericardial disorders, including pericarditis, pericardial effusion and cardiac tamponade.\n\nN. Prior allogeneic stem cell or solid organ transplantation on immunosuppression.\n\nO. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to atezolizumab.\n\nP. Uncontrolled diabetes.\n\nQ. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.\n\nR. Severe infection within four weeks prior to the first IMP administration or the administration of antibiotics within two weeks prior to the first IMP administration, with the exemption of patients requiring prophylaxis.",{"count":126,"type":20},[23,24],"This clinical trial is looking at a drug called atezolizumab. Atezolizumab is approved as standard of care treatment for adult patients with urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma and triple negative breast cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.\n\nAtezolizumab works in patients with these types of cancers which have certain changes in the cancer cells called high tumour mutational burden (TMB) or high microsatellite instability (MSI) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD).\n\nInvestigators now wish to find out if it will be useful in treating patients with other cancer types which are also TMB\u002FMSH-high or show CMMRD. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[45,130,44,50,51,36,97,287,248,288],"Endometrial Neoplasms","Solid Tumours",[30,33,34,36,37,45,46,48,50,51,52,54,56,60,62],{"date":211,"type":71},{"date":292,"type":71},"2023-10-25",{"date":75,"type":20},{"name":77,"class":78},{"id":296,"slug":297,"hasResults":11,"nctId":298,"briefTitle":299,"officialTitle":300,"acronym":4,"eligibilityCriteria":301,"healthyVolunteers":11,"sex":17,"minAge":302,"maxAge":4,"enrollmentInfo":303,"targetDuration":4,"studyType":21,"phases":305,"briefSummary":306,"conditions":307,"keywords":314,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":320,"lastUpdatePostDateStruct":321,"startDateStruct":323,"completionDateStruct":325,"leadSponsor":327,"locationsCount":328},"100519619","phase-1-a-phase-iii-trial-of-aleta-001-for-the-treatment-of-participants-with-b-cell-malignancies-100519619","NCT06045910","A Phase I\u002FII Trial of ALETA-001 for the Treatment of Participants With B-cell Malignancies","A Cancer Research UK Phase I\u002FII Trial of ALETA-001 in Participants Who Have Received an Anti-CD19 CAR T-Cell Therapy for the Treatment of B-cell Malignancies","Inclusion Criteria:\n\nFor all participants\n\nCriteria to be met prior to enrolment in the trial:\n\n* Aged 16 years or over.\n* Written (signed and dated) informed consent and be capable of co-operating with ALETA-001 administration and follow-up.\n* Confirmed diagnosis of B-cell NHL according to World Health Organization (WHO) 2016 criteria.\n* Eastern Cooperative Oncology Group performance status of 0, 1 or 2.\n* Biochemical indices within protocol specified ranges.\n\nCohort Specific Inclusion criteria (for Phase I Cohorts A \\& B) Criteria to be met prior to enrolment in the trial.\n\n* Histologically confirmed diagnosis of relapsed\u002Frefractory LBCL or MCL.\n* Have received an approved anti-CD19 CAR T-cell therapy.\n* Objectively evaluable or measurable disease at 4 weeks (±1 week) post CAR T, which demonstrates:\n\n  * inadequate or incomplete response (PR or SD), or\n  * PD if there is a reasonable expectation of deriving benefit from trial treatment, or\n  * initial response followed by relapse within 9 months assessed according to Lugano Criteria.\n* Haematological indices within protocol specified ranges.\n\nCohort Specific Inclusion criteria (for Phase I Cohorts C \\& D) Criteria to be met prior to lymphodepleting chemotherapy for CAR T therapy.\n\n* Histologically confirmed diagnosis of relapsed\u002Frefractory LBCL or MCL.\n* Approved by the UK national CAR T Clinical Panel (NCCP) to receive an approved anti-CD19 CAR T-cell therapy.\n* Haematological indices within protocol specified ranges.\n* Adequate cardiac function within protocol specified ranges with no clinical symptoms or signs of heart failure.\n* Resting O2 saturation of ≥92% on room air.\n\nEligibility for participants in Phase II of the trial will depend on timing of administration of ALETA-001 which will be recommended by the Safety Review Committee (SRC).\n\nExclusion Criteria for all participants:\n\n* Active or previous malignancies of other types that, in the opinion of the Investigator, should exclude the participant. Exceptions include adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and patients with asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or who require only hormonal therapy and have had normal prostate specific antigen for \\>1 year prior to the start of therapy. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 2 years or more and are deemed at negligible risk for recurrence, are eligible for the trial.\n* Any ongoing toxic manifestation of previous anti-cancer treatment that, in the opinion of the Investigator, should exclude the participant.\n* Ongoing need for systemic immunosuppressive therapy other than replacement dose of corticosteroids. Intermittent topical, inhaled or intranasal corticosteroids are permitted.\n* Presence of active infections and\u002F or inflammatory disease requiring active management.\n* Documented current central nervous system involvement by lymphoma.\n* Women of childbearing potential (or are already pregnant or lactating) unless willing to adhere to protocol-defined contraceptive requirements.\n* Male patients with partners of childbearing potential unless willing to adhere to protocol-defined contraceptive requirements.\n* Major thoracic or abdominal surgery from which the participant has not yet recovered.\n* At high medical risk because of non-malignant systemic disease including active uncontrolled infection.\n* Hypersensitivity to any of the ingredients\u002Fexcipients in ALETA-001.\n* Participation in another interventional clinical trial, whilst taking part in this trial of ALETA-001. Participation in an observational trial or interventional clinical trial that does not involve administration of an IMP and that would not place an unacceptable burden on the participant, in the opinion of the Investigator and CDD, would be acceptable.\n* Participants with any congenital or acquired immunodeficiency syndrome or who are receiving immunosuppressive therapy (including any dose of systemic corticosteroids), or who are immunosuppressed post organ transplant. However, participants receiving inhaled corticosteroids and participants with a history of allergy (other than anaphylaxis) are eligible, as are participants with a history of autoimmune disease.\n* Any other condition that, in the Investigator's opinion, would mean that the trial is not in the best interests of the participant.\n* Concurrent radiotherapy (except for palliative reasons).\n\nCohort specific exclusion criteria prior to enrolment in the trial (for Phase I\n\nCohorts A \\& B):\n\n* Participants who have received any other systemic anti-cancer treatment post-CAR T.\n* Potential participants who experienced any of the following because of the initial CAR T treatment:\n\n  * Grade 4 CRS or ICANS post CAR T infusion.\n  * Grade ≥3 CRS or ICANS persisting beyond 7 days despite optimal therapy.\n  * Any Grade ≥1 CRS or ICANS must have fully resolved.\n* Any Grade ≥3 organ toxicity (other than haematologic toxicity) following CAR T infusion must have improved to Grade ≤2 for at least 48 hours prior to ALETA-001 infusion.\n\nCohort specific exclusion criteria prior to ALETA-001 infusion between Day 10-18 post CAR T-cell infusion (for Phase I Cohorts C \\& D):\n\n* Grade 4 CRS or ICANS post CAR T infusion.\n* Grade ≥3 CRS or ICANS persisting beyond 7 days despite optimal therapy.\n* Any Grade ≥2 CRS or ICANS must have improved to Grade ≤1 for at least 48 hours prior to ALETA-001 infusion.\n* ECOG performance status ≥3.\n* Any Grade ≥3 organ toxicity (other than haematologic toxicity) following CAR T infusion must have improved to Grade ≤2 for at least 48 hours prior to ALETA-001 infusion.\n* Any unresolved serious active infection which in the opinion of the Investigator precludes ALETA-001 infusion (ongoing need for IV antimicrobial therapy per se is not an exclusion).","16 Years",{"count":304,"type":20},84,[91,23],"This is a Phase I\u002FII multicentre, open-label trial designed to evaluate the efficacy, safety, tolerability, timing of administration and pharmacokinetics (PK) of a novel chimeric antigen receptor (CAR) T-cell engager, ALETA-001, administered by intravenous (IV) infusion as a single agent every 2 weeks in participants with B-cell malignancies post CD19 CAR T-cell therapy. This first in human study is divided into 2 parts: a safety lead-in phase (Phase I) and a dose expansion phase (Phase II). Different dose levels of ALETA-001 and timing of administration will be evaluated in Phase I in order to define a recommended dosing level and time of administration for Phase II. Phase II will further evaluate the safety, PK and therapeutic activity of ALETA-001.",[308,309,310,311,312,313],"Lymphoma, Non-Hodgkin","Lymphoma, Large B-Cell, Diffuse","Lymphoma, Mantle-Cell","Lymphoma, Follicular","Lymphoma, B-Cell","Large B-cell Lymphoma",[315,316,317,318,319],"Neoplasms","Immunotherapy, Adoptive","Receptors, Chimeric Antigen","Receptors, Antigen, T-Cell","Antigens, CD19","2025-07-24",{"date":322,"type":71},"2025-07-28",{"date":324,"type":71},"2024-02-07",{"date":326,"type":20},"2029-12-21",{"name":77,"class":78},7,{"id":330,"slug":331,"hasResults":11,"nctId":332,"briefTitle":333,"officialTitle":334,"acronym":4,"eligibilityCriteria":335,"healthyVolunteers":11,"sex":17,"minAge":87,"maxAge":4,"enrollmentInfo":336,"targetDuration":4,"studyType":21,"phases":338,"briefSummary":339,"conditions":340,"keywords":350,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":356,"lastUpdatePostDateStruct":357,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":364},"100511807","phase-1-htl0039732-in-participants-with-advanced-solid-tumours-100511807","NCT05944237","HTL0039732 in Participants With Advanced Solid Tumours","A Cancer Research UK Phase I\u002FIIa Trial of HTL0039732, Given Orally as Monotherapy and in Combination With Immunotherapy or Other Approved Therapies in Participants With Advanced Solid Tumours","Inclusion Criteria:\n\n1. Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product administration and follow-up.\n2. Phase 1, dose escalation phase\n\n   Part A (HTL0039732 monotherapy):\n   * Histologically or cytologically proven advanced solid tumour, refractory to conventional treatment, or for which no further conventional therapy is considered appropriate by the Investigator or is declined by the potential participant.\n   * At least 1 measurable lesion according to RECIST v1.1, which (in the Investigator's opinion) has had objective radiological progression on or after the last therapy, or at least one assessable lesion e.g. pleural or peritoneal thickening that does not fulfil RECIST v1.1 criteria for measurable disease.\n\n     a. Consent for fresh tumour biopsy sample(s) at time of PD, if the participant has accessible disease and is eligible to receive atezolizumab. Optional at time of disease progression.\n   * Consent to access and analysis of any available archival tissue or a fresh tumour sample at baseline, if archival tissue is unavailable.\n   * Consent for fresh tumour biopsy sample(s) at time of PD, if the participant has accessible disease and is eligible to receive atezolizumab. Optional at time of disease progression.\n\n   Phase 1 Part B:\n\n   \\- Histologically proven advanced solid tumour where PGE2\u002FEP4 signalling is believed to be more prevalent or significant (such as microsatellite stable colorectal cancer (MSS CRC), gastro-esophageal cancer, head and neck squamous cell carcinoma (HNSCC), mCRPC, pancreatic cancer, lung cancer, bladder cancer, mesothelioma, cervical cancer, renal cancer, sarcoma, pheochromocytoma and cancers with PI3K\u002FAKT\u002FmTOR pathway activating mutations using a clinically-validated assay).\n\n   Phase 2a:\n\n   \\- Histologically proven advanced solid tumour, in line with indications listed below, refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the potential participant:\n   1. MSS CRC with PIK3CA or HER2 mutation, and\u002For other driver mutation as agreed with the Sponsor (genomic alteration to have been previously identified using a validated next-generation sequencing method performed on either tumour tissue or circulating tumour DNA \\[ctDNA\\]);\n   2. Gastric or gastroesophageal junction (GOJ) adenocarcinoma;\n   3. Clear cell renal cell carcinoma;\n   4. mCRPC\n\n   Phase 1 Part B and Phase 2a:\n   * Consent to access and analysis of any available archival tissue.\n   * Consent for fresh tumour biopsy samples at baseline and on treatment. However, the following exceptions will be permitted if archival tissue is available at the recruiting site:\n\n     1. Patients with mCRPC: biopsies are not required for those whose only safely accessible lesions are bone metastases that lack an accessible soft tissue component.\n     2. For the first 12 participants in each indication: the on-trial biopsy is optional; and the baseline biopsy is mandatory if there is a safely accessible lesion but may be omitted for patients who have no safely accessible lesion, to permit their inclusion in the study. This will continually be assessed through the study.\n   * Disease refractory to conventional treatment, or for which no further conventional therapy is considered appropriate by the Investigator or is declined by the participant.\n   * Except for mCRPC, at least 1 measurable lesion according to RECIST v1.1, which (in the Investigator's opinion) has had objective radiological progression on or after the last therapy. Potential participants with mCRPC may instead have had PD according to PCWG3 criteria.\n\n     1. Previously irradiated lesions cannot be counted as target lesions unless clearly progressed after the radiotherapy.\n     2. Lesions that are intended to be biopsied should not be counted as target lesions (those undergoing biopsy must have at least one target lesion that is not intended to be biopsied).\n   * For indications where anti-PD-1\u002FPD-L1 therapy is standard of care (such as clear cell renal cell carcinoma, or gastric or GOJ adenocarcinoma with elevated PD-L1 expression), patients must have received that therapy and must be considered to have had progressive disease by the Investigator either on, or within 6 months after, that treatment.\n3. Life expectancy of at least 12 weeks.\n4. Eastern Cooperative Oncology Group performance status of 0 or 1.\n5. Haematological and biochemical indices within the protocol specified ranges.\n6. Stable thyroid function tests. Stable doses of thyroxine replacement are permitted.\n7. Aged 18 years or over at the time consent is given.\n\nExclusion Criteria:\n\n1. Radiotherapy (except for palliative reasons), chemotherapy, non chemotherapy systemic anti-cancer therapy (apart from life-long hormone suppression such as luteinising hormone-releasing agents in participants with mCRPC) or investigational medicinal products during the 4 weeks prior to enrolment; or first dose of an immunotherapy during the previous 12 weeks before first dose of HTL0039732.\n2. Ongoing toxic manifestations of previous treatments that are Grade \\>1 per CTCAE v5.0.\n3. Any central nervous system metastases (unless potential participants have had local therapy and are asymptomatic, radiologically stable and have been off steroids for ≥4 weeks prior to enrolment).\n4. Women of child-bearing potential (or who are already pregnant or lactating). Exceptions apply.\n5. Men with partners of childbearing potential. Exceptions apply.\n6. Major thoracic or abdominal surgery from which the potential participant has not yet recovered.\n7. At high medical risk because of non-malignant systemic disease, including active uncontrolled infection.\n8. Known history of current or latent tuberculosis, HIV or Hepatitis B or C infection.\n9. Prior treatment with EP4 inhibitor.\n10. Treatment with selective cyclooxygenase-2 inhibitor in the 8 weeks prior to enrolment.\n11. Known hypersensitivity or intolerance to hydroxypropyl methylcellulose.\n12. Use of systemic immunosuppressive agent in the 2 weeks prior to enrolment. Exceptions apply.\n13. Significant cardiovascular disease.\n14. Known active peptic ulcer disease, or symptoms of gastritis, dyspepsia or gastro-esophageal reflux disease (one or more episodes per week).\n15. Current or planned participation in another interventional clinical trial, whilst taking part in this trial of HTL0039732.\n16. Limited ability to swallow or absorb oral medications.\n17. Any other condition that, in the Investigator's opinion, would mean that the trial is not in the best interests of the potential participant.\n\n    Phase 1 Part B and Phase 2a:\n18. Any live vaccines in the 4 weeks prior to enrolment.\n19. Diagnosis of immunodeficiency.\n20. Active autoimmune disease requiring systemic treatment in the 2 years prior to enrolment.\n21. History or clinical suspicion of interstitial lung disease, history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.\n22. Hypersensitivity to atezolizumab or any of its excipients.\n23. Prior adverse reaction to cancer immunotherapy that required steroid or other immunosuppressive treatment or led to discontinuation of that treatment.",{"count":337,"type":20},150,[91,23],"The purpose of this trial is to evaluate a new drug, HTL0039732, that will be administered on its own (as a monotherapy) and in combination with atezolizumab or with other approved anti-cancer therapies, in participants with advanced solid tumours.",[315,341,342,100,343,97,104,344,345,346,102,347,348,349],"Prostatic Neoplasms, Castration-Resistant","Stomach Neoplasms","Head and Neck Neoplasms","Lung Neoplasms","Urinary Bladder Neoplasms","Mesothelioma, Malignant","Kidney Neoplasms","Sarcoma","Pheochromocytomas",[351,352,353,354,355],"EP4 antagonist","Anti-PD-1\u002FPD-L1 agents","PGE2","EP4","COX inhibitor","2025-06-05",{"date":358,"type":71},"2025-06-08",{"date":360,"type":71},"2023-07-13",{"date":362,"type":20},"2027-06",{"name":77,"class":78},5,{"id":366,"slug":367,"hasResults":11,"nctId":368,"briefTitle":369,"officialTitle":370,"acronym":371,"eligibilityCriteria":372,"healthyVolunteers":11,"sex":17,"minAge":302,"maxAge":4,"enrollmentInfo":373,"targetDuration":4,"studyType":21,"phases":375,"briefSummary":376,"conditions":377,"keywords":379,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":385,"lastUpdatePostDateStruct":386,"startDateStruct":388,"completionDateStruct":390,"leadSponsor":391,"locationsCount":392},"100460214","phase-1-tt-702-in-patients-with-advanced-solid-tumours-100460214","NCT05272709","TT-702 in Patients With Advanced Solid Tumours.","CURATE: A Cancer Research UK Phase I\u002FII, Dose Escalation and Expansion Trial of TT-702, A Selective Adenosine A2BR Antagonist, Given Orally as a Monotherapy Agent and in Combination, in Patients With Advanced Solid Tumours","CURATE","Inclusion criteria:\n\n1. Be able to provide informed consent and be capable of co-operating with IMP administration, procedures and follow-up.\n2. Be willing to provide samples (blood and tissue) as required.\n3. Consent to access any available archival tissue.\n4. Consent for fresh tumour biopsy samples at baseline and on trial (may be Investigator mandated for patients in the dose escalation phase; mandatory for a minimum of eight patients in each expansion cohort). Investigators will consider whether a biopsy is feasible for the patient in the dose escalation phase and this will not impede participation in the trial if biopsy is not a suitable option.\n5. Life expectancy estimated by the Investigator to be at least 12 weeks.\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n7. Cohort 1M\u002F2M (TT-702 monotherapy) - Aged 16 years or over at the time consent is given.\n8. Cohort 1A\u002F2A (TT-702 \\& darolutamide combination cohorts) - Aged 18 years or over at the time consent is given.\n9. Haematological and biochemical indices within the protocol specified ranges.\n10. Objectively or measurable evaluable disease, radiologically according to RECIST Version 1.1 (and\u002For, in mCRPC patients, according to PCWG3 criteria). Has radiological disease progression (and\u002For, in mCRPC patients, PSA progression according to PCWG3 criteria) at the time of study enrolment.\n11. Castrate levels of testosterone (\\\u003C1.7 nmol\u002FL \\[50 ng\u002FdL\\]) (mCRPC patients only).\n\nPhase I, dose escalation phase\n\nHistologically or cytologically proven advanced solid tumours refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient. Phase I dose escalation cohorts are:\n\n* Phase I, Cohort 1M (TT-702 monotherapy cohort): Any solid tumour for which standard of care has been exhausted or, is considered inappropriate for or, declined by the patient.\n* Phase I, Cohort 1A (TT-702 \\& darolutamide combination cohort): mCRPC previously treated with a next generation AR antagonist (including enzalutamide, apalutamide or darolutamide) or abiraterone.\n* Phase I, Cohort 1P (TT-702 \\& PD-1\u002FPD-L1 combination cohort): Patients with PD-1\u002FPD-L1 resistant tumours (i.e. disease progression after a prior PD-1\u002FPD-L1 inhibitor with at least 12 weeks treatment).\n\nPhase II (expansion phase)\n\nHistologically or cytologically proven advanced solid tumour of particular interest based on preclinical and clinical data, refractory to conventional treatment or, for which no conventional therapy is considered appropriate by the Investigator or, is declined by the patient. Phase II expansion cohorts are:\n\n• Cohort 2M (TT-702 Monotherapy expansion cohorts) - mCRPC,TNBC and MMR\u002FMSI defective tumours:\n\nMMR\u002FMSI defective tumours:\n\n* Prior treatment with an anti-PD-1 or anti-PD-L1 agent, either as monotherapy or in combination with other agent(s). This should be the preceding treatment prior to trial entry.\n* Patients must have progressed on an anti-PD-1\u002Fanti-PD-L1 agent.\n* Patients must have experienced Investigator-assessed initial clinical benefit from the most recent anti-PD-1\u002Fanti-PD-L1 treatment (either as monotherapy or in combination with other compounds) for at least 10 weeks. Initial benefit is defined as SD or better with an anti-PD 1\u002Fanti-PD-L1 therapy.\n* Diagnosis of metastatic MSI-H (defined as MSI polymerase chain reaction test with instability shown in ≥2 or ≥30% of microsatellite markers) or metastatic MMRd (defined as loss of MLH1, MSH2, MSH6, and\u002For PMS2 expression is detected) through local testing in NHS lab within UKAS\u002FISO 15198 scope of accreditation.\n\nmCRPC:\n\n* Prior treatment with a next generation hormonal agent.\n* Adenocarcinoma without predominant neuroendocrine or small cell features.\n\nTNBC:\n\n* Human epidermal growth factor receptor 2 negativity (negative immunohistochemistry \\[IHC\\] staining \\[score 0 or 1\\] or negative fluorescence in situ hybridisation based on the American Society of Clinical Oncology\u002FCollege of American Pathologists guidelines and recommendations) and determined through local testing in NHS lab within UKAS\u002FISO 15198 scope of accreditation. Note: patients initially diagnosed with hormone receptor-positive and\u002F or HER2-positive breast cancer OR de novo metastatic patients with a primary tumour hormone receptor-positive (weak positivity or ER negativity and progesterone receptor positivity) considered as nonclinically relevant are eligible if the tumour biopsy obtained from a local recurrence or distant metastasis site confirms the TNBC disease.\n* ER and progesterone receptor negativity (\\\u003C1% positive staining cells in the invasive tumour) determined locally using IHC per American Society of Clinical Oncology\u002FCollege of American Pathologists criteria.\n* Patients who have received prior anti-PD-1\u002Fanti-PD-L1 agent must have experienced Investigator-assessed initial clinical benefit from the most recent anti-PD-1\u002Fanti-PD-L1 treatment (either as monotherapy or in combination with other compounds) for at least 10 weeks, followed by subsequent progression. Initial benefit is defined as SD or better with an anti-PD-1\u002Fanti-PD-L1 therapy.\n\nCohort 2A (TT-702 \\& darolutamide combination cohort): mCRPC.\n\n* Patients with mCRPC must have progressive disease according to PCWG3 criteria.\n* Previously irradiated lesions cannot be counted as target lesions unless clearly progressed after radiotherapy.\n* Patients undergoing biopsy should have at least two lesions, one to be used as a target lesion and one to be biopsied.\n* Cohort 2P (TT-702 \\& PD-1\u002FPD-L1 combination cohort): MMR\u002FMSI defective tumours, TNBC or mCRPC.\n\nExclusion criteria:\n\n1. Radiotherapy (except single fractions for palliative reasons), endocrine therapy during the previous four weeks, immunotherapy and chemotherapy during the previous four weeks(previous six weeks for nitrosoureas, Mitomycin-C) before receiving TT-702. A washout period of eight weeks is required for enzalutamide and apalutamide before the patient receives their first dose of TT-702. A washout period of 4 weeks or 5 half-lives whichever is shorter for any other previous preceding IMPs is required before the patient receives their first dose of TT-702 (in the combination cohorts no washout is needed from PD-1\u002FPD-L1 and darolutamide, respectively).\n2. Patients with ongoing toxic manifestations of previous treatments greater than NCI CTCAE Version 5.0 Grade 1. Exceptions to this are alopecia and any ongoing toxic manifestation which in the opinion of the Investigator should not exclude the patient.\n3. Patients with symptomatic brain or leptomeningeal metastases should be excluded. Asymptomatic patients with previously treated and stable brain metastases (in previous four weeks to study entry) and not requiring any steroids are eligible for the trial. Patients who are stable on anticonvulsants are also eligible.\n4. Cohort 1M\u002F2M (monotherapy) - Women of childbearing potential (or are already pregnant or lactating). However, those patients who meet the following points are considered eligible:\n\n   • Have a negative highly sensitive pregnancy test of a serum sample within 7 days prior to trial inclusion; and\n\n   • Agree to use two forms of medically approved contraception: i. one highly effective form including but not limited to: oral, injected,implanted, transdermal or intravaginal hormonal contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormonereleasing system, bilateral tubal occlusion or vasectomised partner; ii. plus a barrier method (for example, condom plus spermicide); iii. or agree to sexual abstinence. Effective from the first administration of TT-702, throughout the trial and for six months after the last administration of IMP.\n5. Male patients with partners of childbearing potential. However, those patients who meet the following points are considered eligible:\n\n   * Agree to take measures not to father children by using a barrier method of contraception \\[condom plus spermicide\\] or sexual abstinence12 effective from the first administration of IMP throughout the trial and for six months after the last administration of IMP.\n   * Male patients with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicide) to prevent exposure of the foetus or neonate.\n   * Non-vasectomised male patients must also be willing to ensure that any partner of childbearing potential uses a highly effective method of contraception (for example, oral, injected, implanted, transdermal or intravaginal hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system or bilateral tubal occlusion) or agree to sexual abstinence for the same duration.\n6. Major thoracic or abdominal surgery from which the patient has not yet recovered.\n7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. Patients with previous Hepatitis C exposure but no current infection are eligible to participate.\n8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).\n9. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.\n10. Concurrent congestive heart failure, prior history of class II-IV cardiac disease (New York Heart Association \\[NYHA\\]), prior history of clinically significant cardiac ischaemia or prior history of clinically significant cardiac arrhythmia. Patients with significant cardiovascular disease are excluded as defined by:\n\n    1. History of congestive heart failure requiring therapy (NYHA III or IV);\n    2. History of unstable angina pectoris or myocardial infarction up to six months prior to trial entry (patients with previous cardiac or thrombotic events who are now stable and or recovered are eligible);\n    3. Presence of severe valvular heart disease;\n    4. Presence of a ventricular arrhythmia requiring treatment;\n    5. Left ventricular ejection fraction \\\u003C 50%;\n    6. Has a QTcF prolongation to \\>470 milliseconds (ms) based on a 12-lead ECG in triplicate;\n    7. Previous stroke or transient ischaemic attack within 6 months of trial entry;\n    8. History of clinically significant peripheral vascular disease\u002Fvasculitis\u002Fvasculopathy;\n    9. Cohort 1A\u002F2A - A history of QTcF prolongation or Torsade de pointes.\n11. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I\u002FII trial of TT-702. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP and which would not place an unacceptable burden on the patient in the opinion of the Investigator would be acceptable.\n12. Previous malignancies of other types, apart from adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years or more and are deemed at negligible risk for recurrence, are eligible for the trial.\n13. A concomitant significant other illness that might in the opinion of the Investigator affect compliance with the protocol or interpretation of results, examples include but are not limited to autoimmune diseases or immune deficiency, or other disease with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar\u002Fplantar fibromatosis), alcoholic hepatitis, cirrhosis, and inherited liver disease, previous organ transplantation, uncontrolled or poorly controlled diabetes mellitus (for example HbA1c \\>10%) and patients with non-alcoholic steatohepatitis.\n14. History of an immune-mediated adverse event of Grade 3 or above attributed to prior cancer immunotherapy that resulted in permanent discontinuation of the prior immunotherapeutic agent. Immune-mediated adverse events related to prior immunomodulatory therapy (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not either resolved completely to baseline or are Grade ≤2 in severity.\n15. Patients on systemic corticosteroids (apart from replacement doses for endocrinopathy up to an equivalent of 10 mg QD prednisolone). Topical or inhaled steroids for pre-existent diseases are allowed.\n16. Patients who received a live vaccine within 30 days before trial enrolment are excluded.\n17. Patients with a known or suspected history of hypersensitivity or allergy to TT-702, or any of its excipients (for any strength) are excluded:\n\n    * TT-702 10 mg strength, excipients: hydroxypropyl cellulose, sodium lauryl sulfate, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium and magnesium stearate;\n    * TT-702 40 mg strength, excipients: hydroxypropyl cellulose, sodium lauryl sulfate, mannitol, croscarmellose sodium and magnesium stearate;\n    * TT-702 120 mg strength, excipients: poloxamer-188, sodium lauryl sulfate, mannitol, croscarmellose sodium and magnesium stearate in hydroxypropyl methylcellulose (HPMC) capsules;\n    * TT-478 (also known as GS-6201 or CVT-6883).\n18. Cohort 1A\u002F2A (TT-702 \\& darolutamide) - Patients with a known or suspected history of hypersensitivity or allergy to darolutamide or any of its excipients: calcium hydrogen phosphate, croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone, hypromellose, lactose monohydrate, macrogol, and titanium dioxide.\n19. Patients who take therapies that inhibit or induce CYP3A must be excluded.\n20. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.\n\nIf a patient is taking any dietary supplements or complementary medicines\u002Fbotanicals, the Sponsor's Centre for Drug Development (CDD) must be informed at the earliest opportunity both prior to enrolment and during the patient's time on trial.",{"count":374,"type":20},188,[91,23],"This clinical trial is evaluating the drug candidate TT-702 in patients with advanced solid tumours. The main aims of the trial are to determine the maximum dose of TT-702 that can be given safely to patients alone and in combination with other anti-cancer agents.",[378],"Advanced Solid Tumors",[380,381,382,383,384],"Adenosine receptors","MSI Deficient Cancers","MMR Deficient Cancer","Castrate resistant Prostate Cancer","Triple Negative Breast Cancer","2024-05-09",{"date":387,"type":71},"2024-05-13",{"date":389,"type":71},"2022-01-19",{"date":362,"type":20},{"name":77,"class":78},3,""]