Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation

NCT04390243 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: ACCRU-GI-1907NCI-2020-02972ACCRU-GI- 1907P30CA015083
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

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.

Conditions

Locally Advanced Pancreatic Carcinoma; Metastatic Pancreatic Carcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) at 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.

  24 weeks

Secondary Outcomes (5)

• 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

Study Arms (1)

Treatment (encorafenib, binimetinib)

EXPERIMENTAL

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.

Drug: Binimetinib; Drug: Encorafenib

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162, Mektovi

Treatment (encorafenib, binimetinib)

Encorafenib DRUG

Given PO

Also known as: Braftovi, LGX 818, LGX-818, LGX818

Treatment (encorafenib, binimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2. (Form is available on the Academic and Community Cancer Research United \[ACCRU\] web site)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 14 days prior to registration)
• Platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to registration)
• Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)
• Aspartate transaminase (AST) =\< 2.5 x ULN; in participants with liver metastases =\< 5 x ULN (obtained =\< 14 days prior to registration)

You may not qualify if:

• 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
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy. NOTE: Patients known to be human immunodeficiency virus ( HIV) positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \< 6 months prior to registration
• Left ventricular ejection fraction (LVEF) =\< 50% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

binimetinib; encorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Andrew Hendifar, M.D.
• Organization: Cedar Sinai Medical Center

Andrew.Hendifar@cshs.org

310-423-2217

Study Officials

• Andrew E Hendifar

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 15, 2020
• Study Start: November 16, 2020
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: May 6, 2024
• Results First Posted: January 23, 2024

Record last verified: 2023-09

Locations

US (5)