A Phase 2 interventional study of Vemurafenib and Cobimetinib in BRAF V600E Mutation Present and Papillary Craniopharyngioma, sponsored by Alliance for Clinical Trials in Oncology. Active, not recruiting at 106 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 2, Interventional, and Treatment
This phase II trial studies how well vemurafenib and cobimetinib work in treating patients with BRAF V600E mutation positive craniopharyngioma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To determine the activity of BRAF and MEK inhibitor combination in untreated papillary craniopharyngiomas as measured by best response at any time during the first four cycles of BRAF and MEK inhibitor treatment.
II. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas that have progressed after prior radiation treatment with or without surgical resection as measured by best response at any time during the first four cycles of BRAF and MEK inhibitor treatment.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival of patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
II. To determine the toxicity of BRAF/MEK inhibitors in patients with papillary craniopharyngiomas.
III. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas as measured by response of enhancing volume of craniopharyngioma.
IV. To determine the activity of BRAF and MEK inhibitor combination in papillary craniopharyngiomas as measured by response of nonenhancing volume of craniopharyngioma.
V. To determine the overall survival of patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
VI. To determine the duration of response in patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
TERTIARY OBJECTIVES:
I. To evaluate visual fields in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
II. To evaluate pituitary hormone replacement over time in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
III. To evaluate the time to response in patients with papillary craniopharyngiomas receiving BRAF and MEK inhibitors.
IV. To assess toxicity that may be associated with radiotherapy in patients with papillary craniopharyngiomas who have received BRAF/MEK inhibitors.
V. To evaluate molecular biomarkers of response in papillary craniopharyngiomas.
VI. To evaluate circulating tumor cells and cell-free circulating deoxyribonucleic acid (DNA) in patients with papillary craniopharyngiomas.
OUTLINE:
Patients receive vemurafenib orally (PO) twice daily (BID) on day 1-28 and cobimetinib PO once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.
After completion of study treatment, patients with disease progression are followed up every 16 weeks for 2 years and all other patients are followed up every 6 months for 5 years.
65 studies on the registry are indexed under Craniopharyngioma; 21 are open to participants now.
This study's enrollment of 24 is below the median of 41 across 45 interventional studies indexed under Craniopharyngioma.
Browse Craniopharyngioma studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Measurable disease and/or non-measurable disease
Prior treatment
Cohort B: Prior radiation therapy required (any type of prior radiation is allowed)
For patients enrolling on Cohort A or Cohort B:
Comorbid conditions
Concomitant medications
Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.
Drug: Vemurafenib · Drug: Cobimetinib · Other: Laboratory Biomarker Analysis · Other: Quality-of-Life Assessment
Given PO
Given PO
Correlative studies
Ancillary studies
Response Rate
Defined as the number of responses achieved during treatment with BRAF and MEK inhibitors divided by the total number of evaluable patients and assessed by contrast-enhanced magnetic resonance imaging or computed tomography. Point estimates will be generated for response rates within each cohort with corresponding 95% binomial confidence intervals. Simon's two-stage design with one interim analysis for futility will be applied to evaluate response rate within each cohort.
Time frame: Up to 5 years
Progression-free Survival
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months
Time frame: Up to 1 year
Overall Survival
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months.
Time frame: Up to 1 year
| Milestone | Arm A | Arm B |
|---|---|---|
| Started | 19 | 5 |
| Completed | 16 | 5 |
| Not completed | 3 | 0 |
Defined as the number of responses achieved during treatment with BRAF and MEK inhibitors divided by the total number of evaluable patients and assessed by contrast-enhanced magnetic resonance imaging or computed tomography. Point estimates will be generated for response rates within each cohort with corresponding 95% binomial confidence intervals. Simon's two-stage design with one interim analysis for futility will be applied to evaluate response rate within each cohort.
| percentage of participants | Arm A | Arm B |
|---|---|---|
| Response Rate | 94 (70 to 100) | 100 (100 to 100) |
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months
| proportion of participants | Arm A | Arm B |
|---|---|---|
| Progression-free Survival | 0.87 (0.57 to 0.89) | 0.80 (0.52 to 1.00) |
Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates at 12 months.
| proportion of participants | Arm A | Arm B |
|---|---|---|
| Overall Survival | NA (NA to NA) | NA (NA to NA) |
Collected over Up to 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A | 0/17 (0%) | 10/17 (58.8%) | 16/17 (94.1%) |
| Arm B | 0/5 (0%) | 3/5 (60%) | 5/5 (100%) |
| Event | Arm A | Arm B |
|---|---|---|
| Eye disorders - Other, specifyEye disorders | 0/17 | 1/5 |
| Edema limbsGeneral disorders and administration site conditions | 0/17 | 1/5 |
| FeverGeneral disorders and administration site conditions | 1/17 | 1/5 |
| Inj, pois and proced complic - Oth specInjury, poisoning and procedural complications | 0/17 | 1/5 |
| MyositisMusculoskeletal and connective tissue disorders | 0/17 | 1/5 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/17 | 1/5 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 3/17 | 1/5 |
| Skin and subcut tissue disord - Oth specSkin and subcutaneous tissue disorders | 0/17 | 1/5 |
| DehydrationMetabolism and nutrition disorders | 2/17 | 0/5 |
| HyponatremiaMetabolism and nutrition disorders | 2/17 | 0/5 |
| Event | Arm A | Arm B |
|---|---|---|
| FatigueGeneral disorders and administration site conditions | 12/17 | 5/5 |
| CPK increasedInvestigations | 10/17 | 5/5 |
| DiarrheaGastrointestinal disorders | 14/17 | 3/5 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 14/17 | 2/5 |
| Aspartate aminotransferase increasedInvestigations | 11/17 | 3/5 |
| Alanine aminotransferase increasedInvestigations | 9/17 | 3/5 |
| AlopeciaSkin and subcutaneous tissue disorders | 0/17 | 3/5 |
| PhotosensitivitySkin and subcutaneous tissue disorders | 8/17 | 2/5 |
| Blurred visionEye disorders | 6/17 | 2/5 |
| Creatinine increasedInvestigations | 2/17 | 2/5 |
| Age, Continuous(years) | Arm A | Arm B | Total |
|---|---|---|---|
| Median | 49.5 (33.0 to 83.0) | 44.0 (29.0 to 69.0) | 48 (29.0 to 83.0) |
| Sex: Female, Male(Participants) | Arm A | Arm B | Total |
|---|---|---|---|
| Female | 9 | 1 | 10 |
| Male | 7 | 4 | 11 |
| Ethnicity (NIH/OMB)(Participants) | Arm A | Arm B | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 4 | 4 |
| Not Hispanic or Latino | 15 | 1 | 16 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Arm A | Arm B | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 0 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 11 | 2 | 13 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 2 | 3 | 5 |
| ECOG Performance Status(Participants) | Arm A | Arm B | Total |
|---|---|---|---|
| 0 | 15 | 3 | 18 |
| 1 | 1 | 2 | 3 |
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Alliance for Clinical Trials in Oncology