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About
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.
Full 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.
Enrollment
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Inclusion criteria
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:
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)
Uncontrolled hypertension defined as persistent systolic blood pressure >= 150/100 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy
Triplicate average baseline corrected QT (QTc) interval >= 480 ms
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Patients who have had another active malignancy within the past two years are ineligible EXCEPT FOR patients with cervical cancer in situ, in situ carcinoma of the bladder, non-melanoma carcinoma of the skin, or patients who have had therapy with curative intent for breast or prostate cancer, but remain on adjuvant hormonal therapy
Received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic therapy (e.g., erlotinib, cetuximab, bevacizumab etc.), =<14 days (=< 28 days for an antibody-based therapy) prior to registration
Patients who have undergone major surgery (e.g., in-patient procedures) =< 6 weeks prior to registration or who have not recovered from side effects of such procedure
Patients who have had radiotherapy =< 14 days prior to registration or who have not recovered from side effects of such procedure. NOTE: Palliative radiation therapy must be complete 7 days prior to the first dose of study treatment
Patient has not recovered to =< grade 1 from toxic effects of prior therapy before registration. EXCEPTIONS: Stable chronic conditions (=< grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies)
Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation =< 28 days prior to registration.
Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=< 12 weeks) history of a partial or complete bowel obstruction, or other condition that will interfere significantly with the absorption or oral drugs
Known history of acute or chronic pancreatitis
Concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amytrophic lateral sclerosis, spinal muscular atrophy)
History or current evidence of RVO or current risk factors for retinal vein occlusion (RVO) (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
Current use of prohibited medication (including herbal medications, supplements, or foods), or use of prohibited medication =< 7 days prior to registration
History of thromboembolic or cerebrovascular events =< 12 weeks prior to registration. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
Evidence of hepatitis B Virus (HBV) or hepatitis C Virus (HCV) infection.
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6 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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