Vemurafenib and Cobimetinib in Treating Patients with BRAF V600E Mutation Positive Craniopharyngioma
- Conditions
- BRAF V600E Mutation PresentPapillary Craniopharyngioma
- Interventions
- Other: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment
- Registration Number
- NCT03224767
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (vemurafenib, cobimetinib) Laboratory Biomarker Analysis 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. Treatment (vemurafenib, cobimetinib) Quality-of-Life Assessment 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. Treatment (vemurafenib, cobimetinib) Vemurafenib 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. Treatment (vemurafenib, cobimetinib) Cobimetinib 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.
- Primary Outcome Measures
Name Time Method Response rate Up to 5 years 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.
- Secondary Outcome Measures
Name Time Method Progression-free survival Up to 5 years Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.
Overall survival Up to 5 years Will be summarized for each cohort within each cohort with Kaplan-Meier curves and estimates.
Trial Locations
- Locations (106)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Mills-Peninsula Medical Center
🇺🇸Burlingame, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸Mountain View, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Scroll for more (96 remaining)University of Alabama at Birmingham Cancer Center🇺🇸Birmingham, Alabama, United States