Targeted drug cobimetinib tested for rare immune cell cancers
NCT ID NCT04079179
First seen Jun 26, 2026 · Last updated Jun 26, 2026
Summary
This phase 2 study tests the drug cobimetinib in children and adults with Langerhans cell histiocytosis and related disorders that have come back or not responded to standard treatment. Cobimetinib blocks a growth signal that goes haywire in these diseases. The study will enroll 90 participants across four groups and measure how well the drug controls the disease over one year.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Cobimetinib (a targeted cancer drug that blocks a protein called MEK)
- What this could lead to
- If it works, this could offer a new treatment option for people with hard-to-treat histiocytic disorders, potentially controlling the disease and slowing neurodegeneration.
- What could go wrong
- This is a mid-stage trial with only 90 participants, so results may not apply to everyone. The drug may cause side effects and may not work for all types of histiocytosis.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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About 90 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Apr 2021
- Expected to finish
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Dec 2029
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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Children (under 18), adults (18 to 64) and older adults (65 and over)
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
INCLUSION CRITERIA: Age at study entry * For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment * For Group 2: Participant may be at least 6 months of age at the time of enrollment * For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment * For Group 4: Participant must be 21 years of age or older at the time of enrollment * 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. * Biopsy proven LCH -AND * Failure of at least front-line therapy for LCH with evaluable disease. -OR * Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR * Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as: * ANC ≥ 0.75 x 10\^9/L (unsupported/without growth factor stimulant) * Platelet count ≥ 75 x 10\^9/L (unsupported/without transfusion within the past 7 days). * Patients with marrow disease must have platelet count of \>/= 75 x 10\^9/L (transfusion support allowed) and must not be refractory to platelet transfusions. * Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days) * Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as: \- Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m\^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to \< 6 years: Male 0.8 mg/dL, Female 0.8; 6 to \< 10 years: Male 1 mg/dL,Female 1; 10 to \< 13 years: Male 1.2 mg/dL; Female 1.2; 13 to \< 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as: * Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age * AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement) * Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as: \- 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 Pregnancy/Birth Control * 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. * 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/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA: \- Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting 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. * 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. * Radiation therapy within the 14 days prior to enrollment. * Any prior treatment with Cobimetinib. * 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. * Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or \< 5 half-lives, whichever is longer, prior to study enrollment. * 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. * For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment. * Corticosteroid therapy less than or equal to 0.5 mg/kg/day 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. * Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug. * Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease. * Exclusions for other illness * Other active malignancy or history of secondary malignancy. * Refractory nausea and vomiting, malabsorption, external biliary shunt * 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. * 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). * History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease. * History of pneumonitis. * 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. * History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible. * 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. * History of clinically significant cardiac dysfunction, including the following: * Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded. * Unstable arrhythmia * Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment * Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher * Myocardial infarction within 3 months prior to initiation of study treatment * Known chronic human immunodeficiency virus (HIV). * History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment. * 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.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
11 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Arkansas Children's Hospital
RECRUITINGLittle Rock, Arkansas, 72202, United States
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Children's Hospital of Orange County
RECRUITINGOrange, California, 92868, United States
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Children's Medical Center- UTSW
RECRUITINGDallas, Texas, 75235, United States
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Children's National Hospital
RECRUITINGWashington D.C., District of Columbia, 20010, United States
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Dana Farber Cancer Institute, Boston Children's
RECRUITINGBoston, Massachusetts, 02215, United States
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John Hopkins University School of Medicine
RECRUITINGBaltimore, Maryland, 21287, United States
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Memorial Sloan Kettering Cancer Center
RECRUITINGNew York, New York, 10065, United States
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NACHO Consortium
NOT_YET_RECRUITINGMemphis, Tennessee, 38105, United States
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Phoenix Children's Hospital
RECRUITINGPhoenix, Arizona, 85016, United States
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Texas Children's Hospital
RECRUITINGHouston, Texas, 77030, United States
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UCSF Benioff Children's Hospital
RECRUITINGSan Francisco, California, 94158, United States
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University of Wisconsin-American Family Children's Hospital
TERMINATEDMadison, Wisconsin, 53792, United States
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