[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"erdheim-chester-disease\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:erdheim-chester-disease":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,6,0,[8,48,112,146,171,197],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":22,"conditions":23,"keywords":30,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100509575","histiocytic-disorder-follow-up-study-100509575",false,"NCT05915208","Histiocytic Disorder Follow-up Study","Inclusion Criteria:\n\n* diagnosis of histiocytic disorder at any age\n\n  1. Langerhans cell histiocytosis,\n  2. Erdheim-Chester disease,\n  3. Rosai-Dorfman disease,\n  4. Xanthogranuloma,\n  5. Mixed histiocytosis\n  6. Malignant histiocytosis (Histiocytic sarcoma, langerhans cell sarcoma, interdigitating cell sarcoma)\n  7. Hemophagocytic lymphohistiocytosis\n\nExclusion Criteria:\n\n* None","ALL","0 Years","89 Years",{"count":19,"type":20},6000,"ESTIMATED","OBSERVATIONAL","The purpose of the study is to describe the burden of chronic health conditions, psychological dysfunction, chronic pain, healthcare utilization, worse health-related quality of life, overall mortality, and cause-specific mortality among individuals with histiocytic disorders",[24,25,26,27,28,29],"Histiocytosis","Langerhans Cell Histiocytosis","Erdheim-Chester Disease","Rosai Dorfman Disease","Xanthogranuloma","Malignant Histiocytoses",[31,32,33,34],"survivorship","long-term","targeted therapy","second cancer","RECRUITING","2026-06-10",{"date":38,"type":39},"2026-06-12","ACTUAL",{"date":41,"type":39},"2022-09-01",{"date":43,"type":20},"2028-12",{"name":45,"class":46},"University of Alabama at Birmingham","OTHER",1,{"id":49,"slug":50,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":54,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":15,"minAge":56,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":59,"phases":60,"briefSummary":63,"conditions":64,"keywords":83,"overallStatus":101,"whyStopped":4,"lastUpdateSubmitDate":102,"lastUpdatePostDateStruct":103,"startDateStruct":105,"completionDateStruct":107,"leadSponsor":109,"locationsCount":111},"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.","DETERMINE","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":58,"type":20},30,"INTERVENTIONAL",[61,62],"PHASE2","PHASE3","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.",[65,66,67,68,69,70,71,72,73,26,74,75,76,77,78,79,80,81,82],"Haematological Malignancy","Malignant Neoplasm","Lymphoproliferative Disorders","Neoplasms by Histologic Type","Neoplasms by Site","Gastrointestinal Cancer","Non-Melanoma Skin Cancer (NMSC)","Langerhans Cell Histiocytosis (LCH)","Cancer","Thyroid Carcinoma, Papillary","Ovarian Neoplasms","Colorectal Neoplasms","Laryngeal Neoplasms","Carcinoma, Non-Small Cell-Lung","Glioma","Multiple Myeloma","Thyroid Carcinoma, Anaplastic","Solid Tumour",[84,85,73,86,87,88,89,90,91,92,69,93,94,95,96,97,98,99,100],"Adult","Antineoplastic Agents","Child","Dabrafenib","Malignancy","Malignant Neoplasms","Molecular Targeted Therapy","Mutation","Neoplasms by Histologic Site","Paediatric","Precision Medicine","Proto-Oncogene Proteins B-raf","Protein Kinase Inhibitors","Rare","Trametinib","Tumour-Agnostic","Young adult","NOT_YET_RECRUITING","2026-02-23",{"date":104,"type":39},"2026-02-27",{"date":106,"type":20},"2026-02",{"date":108,"type":20},"2029-10",{"name":110,"class":46},"Cancer Research UK",27,{"id":113,"slug":114,"hasResults":11,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":4,"eligibilityCriteria":118,"healthyVolunteers":11,"sex":15,"minAge":119,"maxAge":4,"enrollmentInfo":120,"targetDuration":4,"studyType":59,"phases":121,"briefSummary":123,"conditions":124,"keywords":128,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":138,"lastUpdatePostDateStruct":139,"startDateStruct":141,"completionDateStruct":143,"leadSponsor":145,"locationsCount":47},"100446430","early-phase-1-in-human-cxcr4-imaging-of-hematologic-and-solid-tumors-using-68ga-pentixafor-pet-100446430","NCT05093335","In-Human CXCR4 Imaging of Hematologic and Solid Tumors Using [68Ga]-Pentixafor-PET","In-human CXCR4 Imaging of Hematologic and Solid Tumors Using [68Ga]-Pentixafor-PET","Inclusion Criteria:\n\nTwenty patients with histologically proven treatment-naïve, therapy-refractory or relapsed blood cancers meeting the below criteria will be included:\n\n* Indolent B- or T-cell Non-Hodgkin lymphoma (including cutaneous lymphomas) or Non-Hodgkin lymphoma with variable FDG uptake and clinical course, such as mantle cell lymphoma; and measurable disease according to Lugano criteria\n\nor\n\n* Histiocytic neoplasms (Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD) and\u002For Rosai-Dorfman disease (RDD)\n* MGUS\u002FSMM or MM according to IMWG definitions\n* Solid tumors, such as lung cancers, meningioma, adrenocortical neoplasms including cortisol-producing adenomas or high suspicion for tumor, such as in patients with Cushing's disease.\n* Age ≥18\n* Negative serum pregnancy test for female volunteers of childbearing age and potential (as defined by MSKCC Standards \\& Guidelines) from assays obtained \\\u003C2 weeks prior to study enrollment\u002Fintervention; or negative urine pregnancy test performed on the day of intervention\n* MSKCC patients\n\nExclusion Criteria:\n\n* Breast-feeding\n* History of renal functional disorders (chronic kidney disease with eGFR\\\u003C30)\n* Refusal or inability to tolerate the scanning procedure (e.g., due to claustrophobia)","18 Years",{"count":58,"type":20},[122],"EARLY_PHASE1","The purpose of this study is to determine the uptake of the imaging agent \\[68Ga\\]-pentixafor with PET\u002FCT scans in people with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and non-Hodgkin lymphoma (NHL), or you have histiocytic neoplasms (Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD) and\u002For Rosai-Dorfman disease (RDD).",[125,80,126,26,127],"Non-Hodgkin Lymphoma","Histiocytic Neoplasms","Rosai-Dorfman Disease",[129,130,131,132,133,134,135,136,137],"[68Ga]-Pentixafor","PET\u002FCT scan","In-human CXCR4 Imaging","21-356","Symptomatic multiple myeloma","pre-cursor myeloma","MGUS","SMM","Memorial Sloan Kettering Cancer Center","2026-02-04",{"date":140,"type":39},"2026-02-05",{"date":142,"type":39},"2021-10-01",{"date":144,"type":20},"2027-10",{"name":137,"class":46},{"id":147,"slug":148,"hasResults":11,"nctId":149,"briefTitle":150,"officialTitle":150,"acronym":4,"eligibilityCriteria":151,"healthyVolunteers":11,"sex":15,"minAge":119,"maxAge":4,"enrollmentInfo":152,"targetDuration":154,"studyType":21,"phases":4,"briefSummary":155,"conditions":156,"keywords":157,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":163,"lastUpdatePostDateStruct":164,"startDateStruct":166,"completionDateStruct":168,"leadSponsor":170,"locationsCount":47},"100311045","registry-for-patients-with-erdheim-chester-disease-and-other-histiocytoses-100311045","NCT03329274","Registry for Patients With Erdheim-Chester Disease and Other Histiocytoses","Inclusion Criteria:\n\n* Diagnosis of Erdheim-Chester Disease, Langerhans cell histiocytosis, Rosai Dorfman disease, or another histiocytic neoplasm by either 1) documented histopathologic establishing ECD or HN or 2) documented histopathologic findings compatible with Erdheim-Chester disease or HN in the context of corroborating clinical and\u002For radiologic findings or 3) documented radiologic findings, in the absence of a biopsy having been performed or yielding evaluable tissue, that are felt by the Principal Investigator to unequivocally represent an ECD\u002FHN diagnosis given the clinical context or 4) self reported with supporting documentation upon medical record collection.\n* Proficiency in English, in the determination of the Investigator or by self report.\n* Willing to have historical and future HN-related health records sent to Registry review.\n\nExclusion Criteria:\n\n* Patients unwilling to sign consent.\n* Participants under the age of 18.",{"count":153,"type":20},500,"3 Years","The investigators want to understand more about what kinds of health problems are caused by histiocytosis, what happens as a result of different treatments, and how ECD affects people's lives, their feelings and their attitudes. The investigators also want to learn how these things change over time for people with these conditions. To try to figure this out, doctors would like to collect information about people who have histiocytosis and how they are treated for this disease.\n\nSome participants will be asked to complete a brief interview over the telephone. Only a limited number of interviews will take place, and not everyone will be asked to participate in the interview. It is okay if the participant does not want to participate in the interview portion. If this is the case, the participant should let the study team member know when contacted.",[26],[158,159,160,161,162],"registry","Other Histiocytoses","Langerhans cell histiocytosis","Rosai Dorfman disease","17-516","2026-01-06",{"date":165,"type":39},"2026-01-08",{"date":167,"type":39},"2017-10-26",{"date":169,"type":20},"2026-10",{"name":137,"class":46},{"id":172,"slug":173,"hasResults":11,"nctId":174,"briefTitle":175,"officialTitle":176,"acronym":54,"eligibilityCriteria":177,"healthyVolunteers":11,"sex":15,"minAge":119,"maxAge":4,"enrollmentInfo":178,"targetDuration":4,"studyType":59,"phases":179,"briefSummary":180,"conditions":181,"keywords":185,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":190,"startDateStruct":192,"completionDateStruct":194,"leadSponsor":195,"locationsCount":196},"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":58,"type":20},[61,62],"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.",[65,182,183,75,76,77,184,79,80,26,81,82],"Melanoma","Thyroid Cancer, Papillary","Carcinoma, Non-Small-Cell Lung",[84,85,73,88,89,90,91,68,69,94,186,95,97,187,188],"Cobimetinib","Tumour-agnostic","Vemurafenib","2025-11-19",{"date":191,"type":39},"2025-11-24",{"date":193,"type":39},"2023-03-01",{"date":108,"type":20},{"name":110,"class":46},16,{"id":198,"slug":199,"hasResults":11,"nctId":200,"briefTitle":201,"officialTitle":202,"acronym":203,"eligibilityCriteria":204,"healthyVolunteers":11,"sex":15,"minAge":4,"maxAge":4,"enrollmentInfo":205,"targetDuration":4,"studyType":59,"phases":207,"briefSummary":208,"conditions":209,"keywords":215,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":216,"lastUpdatePostDateStruct":217,"startDateStruct":219,"completionDateStruct":221,"leadSponsor":223,"locationsCount":225},"100368581","phase-2-cobimetinib-in-refractory-langerhans-cell-histiocytosis-lch-and-other-histiocytic-disorders-100368581","NCT04079179","Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders","A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders.","NACHO-COBI","INCLUSION CRITERIA:\n\nAge at study entry\n\n* For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment\n* For Group 2: Participant may be at least 6 months of age at the time of enrollment\n* For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment\n* For Group 4: Participant must be 21 years of age or older at the time of enrollment\n* Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.\n* Biopsy proven LCH -AND\n* Failure of at least front-line therapy for LCH with evaluable disease. -OR\n* Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR\n* Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed\u002Frefractory disease) with evaluable active disease.\n\nPerformance Level:\n\n-Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.\n\nAdequate Hematologic Function Defined as:\n\n* ANC ≥ 0.75 x 10\\^9\u002FL (unsupported\u002Fwithout growth factor stimulant)\n* Platelet count ≥ 75 x 10\\^9\u002FL (unsupported\u002Fwithout transfusion within the past 7 days).\n* Patients with marrow disease must have platelet count of \\>\u002F= 75 x 10\\^9\u002FL (transfusion support allowed) and must not be refractory to platelet transfusions.\n* Hemoglobin ≥ 8 g\u002FdL (unsupported\u002Fwithout transfusion within the past 7 days)\n* Patients with marrow disease must have hemoglobin ≥ 8 g\u002FdL (transfusion support allowed).\n\nAdequate Renal Function Defined as:\n\n\\- Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL\u002Fmin\u002F1.73m\\^2 or serum creatinine based on age\u002Fgender as follows:\n\nMaximum Serum Creatinine (mg\u002FdL) Age 2 to \\\u003C 6 years: Male 0.8 mg\u002FdL, Female 0.8; 6 to \\\u003C 10 years: Male 1 mg\u002FdL,Female 1; 10 to \\\u003C 13 years: Male 1.2 mg\u002FdL; Female 1.2; 13 to \\\u003C 16 years: Male 1.5 mg\u002FdL ; Female 1.4; ≥ 16 years: Male 1.7 mg\u002FdL; Female 1.4;\n\nAdequate Liver Function Defined as:\n\n* Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age\n* AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)\n* Serum albumin ≥ 2 g\u002FdL.\n\nFor patients with liver disease caused by histiocytic disorder:\n\n• Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease.\n\nAdequate Cardiac Function Defined as:\n\n\\- Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above\n\nPregnancy\u002FBirth Control\n\n* Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.\n* Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and\u002For potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control.\n\nEXCLUSION CRITERIA:\n\n\\- Prior and Concomitant Use of Drugs with CYP3A4 inducing\u002Finhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.\n\n* Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately. See below for specific consideration of prednisone and corticosteroids prior to enrollment.\n\n  * Radiation therapy within the 14 days prior to enrollment.\n  * Any prior treatment with Cobimetinib.\n  * Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.\n  * Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or \\\u003C 5 half-lives, whichever is longer, prior to study enrollment.\n  * Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.\n  * For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.\n  * Corticosteroid therapy less than or equal to 0.5 mg\u002Fkg\u002Fday averaged during the 28 days prior to study enrollment is permissible. Patients receiving corticosteroids must be on a stable or decreasing dose for 14 days prior to enrollment and discontinue once study treatment has started.\n  * Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.\n  * Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.\n* Exclusions for other illness\n\n  * Other active malignancy or history of secondary malignancy.\n  * Refractory nausea and vomiting, malabsorption, external biliary shunt\n  * Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.\n  * Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).\n  * History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.\n  * History of pneumonitis.\n  * Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure \\> 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.\n  * History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.\n  * Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.\n* History of clinically significant cardiac dysfunction, including the following:\n\n  * Clinically significant cardiac arrhythmias including brady-arrhythmias and\u002For patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.\n  * Unstable arrhythmia\n  * Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment\n  * Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher\n  * Myocardial infarction within 3 months prior to initiation of study treatment\n* Known chronic human immunodeficiency virus (HIV).\n* History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.\n* Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.",{"count":206,"type":20},90,[61],"This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.",[210,211,26,27,212,213,214],"Langerhan's Cell Histiocytosis","Juvenile Xanthogranuloma","Neuro-Degenerative Disease","Histiocytic Sarcoma","Histiocytic Disorders, Malignant",[186,72],"2025-09-12",{"date":218,"type":39},"2025-09-18",{"date":220,"type":39},"2021-04-19",{"date":222,"type":20},"2029-12",{"name":224,"class":46},"Carl Allen",12]