BrafPanc: A Phase II Trial of Binimetinib in Combination With Encorafenib in Patients With Pancreatic Malignancies and a Somatic BRAFV600E Mutation
Overview
- Phase
- Phase 2
- Intervention
- Binimetinib
- Conditions
- Locally Advanced Pancreatic Carcinoma
- Sponsor
- Academic and Community Cancer Research United
- Enrollment
- 6
- Locations
- 5
- Primary Endpoint
- Objective Response Rate (ORR) at 24 Weeks
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This phase II trial studies the side effects and how well the combination of binimetinib and encorafenib work in treating patients with pancreatic cancer with a somatic BRAF V600E mutation. Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may work better compared to the usual treatment in treating patients with pancreatic cancer and a somatic BRAF V600E mutation.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the efficacy of the combination of binimetinib and encorafenib as \>= 2nd line of treatment for patients with metastatic pancreatic cancer with BRAF V600E mutation. SECONDARY OBJECTIVES: I. To determine in patients treated with the combination of binimetinib and encorafenib as \>= 2nd line of treatment for patients with metastatic pancreatic cancer with BRAF V600E mutation: Ia. The median progression-free survival. Ib. The median overall survival. Ic. Duration of response. Id. Time to response. Ie. The safety and tolerability. OUTLINE: Patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-25. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION:
- •Histological confirmation of a pancreatic malignancy as confirmed by the local pathology lab
- •Patients whose disease has progressed on (or who were intolerant of) at least one line of therapy for metastatic disease
- •Patients whose disease has recurred with metastatic disease =\< 12 weeks of completion of neoadjuvant or adjuvant systemic chemotherapy; or patients with locally advanced disease whose disease progressed to metastatic disease on, or =\< 12 weeks after completion of systemic chemotherapy would also be eligible
- •Provide informed written consent =\< 28 days prior to pre-registration
- •Central electronic/paper confirmation of the presence of a BRAF V600E mutation. This review is mandatory prior to pre-registration to confirm eligibility. Results from a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) certified testing lab (commercial or institutional) that confirm the presence of a BRAF V600E mutation in the patient's tumor must be submitted for central review
- •REGISTRATION: NOTE: Registration must occur =\< 30 days after pre-registration
- •Confirmation of the presence of BRAF V600E mutation in the patient's tumor
- •Measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or
Exclusion Criteria
- •REGISTRATION:
- •Patients whose tumor harbors a BRAF non-V600E mutation or a BRAF fusion
- •Prior therapy with BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib)
- •Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
- •Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •NOTE: Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and to not donate ova from screening until 30 days after the last dose of study drug
- •NOTE: Male participants must agree to use methods of contraception that are highly effective or acceptable, and to not donate sperm from screening until 90 days after the last dose of study drug
Arms & Interventions
Treatment (encorafenib, binimetinib)
Patients receive encorafenib PO QD and binimetinib PO BID on days 1-25. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Binimetinib
Treatment (encorafenib, binimetinib)
Patients receive encorafenib PO QD and binimetinib PO BID on days 1-25. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Encorafenib
Outcomes
Primary Outcomes
Objective Response Rate (ORR) at 24 Weeks
Time Frame: 24 weeks
An objective response is defined as a complete or partial response with a confirmation scan not less than 4 weeks after the initial scan. Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. The final ORR point estimate and corresponding 95% confidence interval will be reported.
Secondary Outcomes
- Progression-free Survival (PFS)(25 months)
- Overall Survival(25 months)
- Duration of Response(12 months)
- Time to Response(25 months)
- Number of Patients With Grade 3+ Adverse Events(25 months)