[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100552268":3},{"organization":4,"armGroups":7,"interventions":20,"overallOfficials":26,"centralContacts":31,"locations":26,"responsibleParty":40,"collaborators":42,"id":47,"slug":48,"hasResults":49,"nctId":50,"briefTitle":51,"officialTitle":51,"acronym":52,"eligibilityCriteria":53,"healthyVolunteers":49,"sex":54,"minAge":55,"maxAge":26,"enrollmentInfo":56,"targetDuration":26,"studyType":59,"phases":60,"briefSummary":62,"conditions":63,"keywords":65,"overallStatus":66,"whyStopped":26,"lastUpdateSubmitDate":67,"lastUpdatePostDateStruct":68,"startDateStruct":71,"completionDateStruct":73,"leadSponsor":75,"locationsCount":26},{"fullName":5,"class":6},"The Christie NHS Foundation Trust","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"ARM A: Standard of care","ACTIVE_COMPARATOR","Continuous dosing of encorafenib 450mg once daily plus binimetinib 45mg twice daily.",[13],"Drug: Standard of Care",{"label":15,"type":16,"description":17,"interventionNames":18},"ARM B: Adaptive therapy","EXPERIMENTAL","4 weeks of encorafenib 450mg once daily plus binimetinib 45mg twice daily, followed by adaptive cycles based on ctDNA TAB level",[19],"Drug: Adaptive Therapy",[21,27],{"type":22,"name":23,"description":24,"armGroupLabels":25,"otherNames":26},"DRUG","Adaptive Therapy","A blood test that measures the amount of tumour DNA circulating in the patient's blood (known as ctDNA) will be conducted every two weeks to check if the cancer cells are still present, and if they are becoming active. The result of this test will allow doctors to monitor the activity of the tumour and judge when to pause and resume encorafenib and binimetinib treatment. This intermittent treatment is called 'adaptive therapy'.",[15],null,{"type":22,"name":28,"description":29,"armGroupLabels":30,"otherNames":26},"Standard of Care","Encorafenib and binimetinib delivered to UK standard of care.",[9],[32,37],{"name":33,"role":34,"phone":35,"phoneExt":26,"email":36},"Trial Project Manager","CONTACT","0000","dynamic_study@liverpool.ac.uk",{"name":38,"role":34,"phone":26,"phoneExt":26,"email":39},"Research Group Project Manager","translationalmelanoma@manchester.ac.uk",{"type":41,"investigatorFullName":26,"investigatorTitle":26,"investigatorAffiliation":26,"oldNameTitle":26,"oldOrganization":26},"SPONSOR",[43,45],{"name":44,"class":6},"University of Manchester",{"name":46,"class":6},"University of Liverpool","100552268","phase-2-circulating-tumour-dna-guided-adaptive-braf-and-mek-inhibitor-therapy-100552268",false,"NCT06470880","Circulating Tumour DNA Guided Adaptive BRAF and MEK Inhibitor Therapy","DyNAMIc","Inclusion Criteria\n\nAt Screening\n\n1. Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study\n2. Histological confirmation of cutaneous melanoma\n3. ≥ 18 years of age\n4. Stage III un-resectable\u002F IV disease\n5. Measurable disease on CT (thorax, abdomen and pelvis, ± neck if indicated) and\u002For PET-CT, and CT or MRI (brain) scan (RECIST v1.1)\n6. BRAF p.V600E\u002FK\u002FR\u002FD mutation confirmed (exact point mutation must be known)\n7. ECOG performance status 0\u002F1\u002F2\n8. Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to the first dose of study drugs\n9. Adequate organ function as defined below:\n\n   i. Haemoglobin ≥ 9 g\u002FdL ii. White blood count ≥ 2 x109\u002FL iii. ANCa ≥ 1.2 x109\u002FL iv. Platelet count ≥ 75 x109\u002FL v. Albumin ≥ 2.5 g\u002FdL vi. Total bilirubinb ≤ 1.5 x ULNa vii. ASTa or ALTa ≤ 3 x ULNa viii. Calculated creatinine clearance ≥ 30ml\u002Fmin\n10. Women of childbearing potential participating in the study (WOCBP see Appendix B for definition) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of HCG) within 72 hours prior to the start of study drug.\n11. WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs plus at least 28 days following last dose of drug (either encorafenib or binimetinib), (see Appendix B).\n12. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 90 days (duration of sperm turnover) from last dose of drug (either encorafenib or binimetinib), (see Appendix B).\n\n    At randomisation:\n13. Left Ventricular Ejection fraction (LVEF) ≥ 50% or ≥LLNa by ECHO\n14. BRAF ctDNA TAB level of ≥15 copies\u002Fml of plasma\n\nExclusion Criteria\n\n1. Prior systemic targeted BRAF\u002FMEKi therapy for stage IV (metastatic) melanoma (treatment for stage III allowed as long as RFS ≥26 weeks following discontinuation of drugs)\n2. BRAF wild-type malignant melanoma\n3. Metastasis to the brain or leptomeninges\n4. Any contraindication to treatment with encorafenib or binimetinib as per the local Summary of Product Characteristics\n5. Hypersensitivity to the active substance or to any of the excipients of encorafenib or binimetinib\n6. Current use of a prohibited medication as described in Section 8.9\n7. History of another malignancy. Exception: Patients who have been disease-free for 3 years, (i.e. patients with second malignancies that are indolent or definitively treated at least 3 years ago), curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS); stage 1, grade I endometrial carcinoma, or patients with a history of completely resected non-melanoma skin cancer. No additional therapy should be required whilst the patient is on study\n8. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures\n9. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection\n10. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption\n11. Child Pugh B or C liver disease\n12. Coronary syndromes (including myocardial infarction within 6 months or unstable angina)\n13. A history or evidence of current ≥ Class II congestive heart failure as defined by the NYHA guidelines with an ejection fraction of \\\u003C50% (see appendix C)\n14. Treatment refractory hypertension defined as a blood pressure of systolic \\>150 mmHg and\u002For diastolic \\>95 mm Hg on \\>3 occasions which cannot be controlled by anti-hypertensive therapy\n15. Uncorrectable electrolyte abnormalities \\> CTCAE v5 Grade 1 (e.g. hypokalaemia, hypomagnesaemia, hypocalcaemia), long QT syndrome (baseline 1 QTC interval ≥ 480msec) or taking medicinal products known to prolong the QT interval\n16. A history or current evidence\u002Frisk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)\n17. Females who are pregnant or breast-feeding and are not able to stop breast-feeding prior to first dose of study drugs (see section 7.5)\n18. Prisoners or patients who are involuntarily incarcerated\n19. Patients who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness","ALL","18 Years",{"count":57,"type":58},40,"ESTIMATED","INTERVENTIONAL",[61],"PHASE2","The goal of this clinical trial is to investigate adaptive therapy in late-stage cutaneous melanoma. The main question it aims to answer are:\n\nIf the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour less resistant to the treatment, an increasing the time it takes for the disease to progress?\n\nParticipants will\n\n* Receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first.\n* Attend fortnightly visits to hospital.\n* Complete EORTC QLQ-C30 and PRO-CTCAE questionnaires, prior to treatment, every 12 weeks and at the point of cancer progression, to assess quality of life.\n\nResearchers will compare the adaptive therapy participant arm with a standard of care arm to answer the research question described above.",[64],"Melanoma",[23],"NOT_YET_RECRUITING","2024-06-17",{"date":69,"type":70},"2024-06-24","ACTUAL",{"date":72,"type":58},"2024-06",{"date":74,"type":58},"2027-06",{"name":5,"class":6}]