Clinical Trials /

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

NCT04390243

Description:

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.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation
  • Official Title: BrafPanc: A Phase II Trial of Binimetinib in Combination With Encorafenib in Patients With Pancreatic Malignancies and a Somatic BRAFV600E Mutation

Clinical Trial IDs

  • ORG STUDY ID: ACCRU-GI-1907
  • SECONDARY ID: NCI-2020-02972
  • SECONDARY ID: ACCRU-GI- 1907
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04390243

Conditions

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

Interventions

DrugSynonymsArms
BinimetinibARRY-162, ARRY-438162, MEK162, MektoviTreatment (encorafenib, binimetinib)
EncorafenibBraftovi, LGX 818, LGX-818, LGX818Treatment (encorafenib, binimetinib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (encorafenib, binimetinib)ExperimentalPatients 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.
  • Binimetinib
  • Encorafenib

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 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)

          -  Aminotransferase (ALT) =< 2.5 x ULN; in participants with liver metastases =< 5 x ULN
             (obtained =< 14 days prior to registration)

          -  Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft Gault formula
             (obtained =< 14 days prior to registration)

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study). Note: During the active monitoring phase of a study (i.e., active
             treatment), participants must be willing to return to the consenting institution for
             follow-up

          -  Ability to swallow the investigational product tablets and capsules

          -  Willing to provide tissue and blood samples for correlative research purposes

        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

          -  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.

               -  NOTE: Patients with previously treated brain metastases may participate provided
                  they are stable (e.g., without evidence of progression by radiographic imaging
                  for =< 28 days prior to registration and neurologic symptoms have returned to
                  baseline), and have no evidence of new or enlarging brain metastases or central
                  nervous system (CNS) edema, and does not require steroids at least 7 days before
                  the first dose of study treatment.

          -  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.

               -  NOTE: Patients with either deep vein thrombosis or pulmonary emobli that do not
                  result in hemodynamic instability are allowed to enroll as long as they are on a
                  stable dose of anticoagulants for =< 4 weeks prior to registration

               -  NOTE: Patients with thromboembolic events related to indwelling catheters or
                  other procedures may register

          -  Evidence of hepatitis B Virus (HBV) or hepatitis C Virus (HCV) infection.

               -  NOTE: Patients with laboratory evidence of cleared HBV or HCV infection may
                  register.

               -  NOTE: Patients with no prior history of HBV infection who have been vaccinated
                  against HBV and who have a positive antibody against hepatitis B surface antigen
                  as the only evidence of prior exposure may register
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:At 24 weeks
Safety Issue:
Description: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 Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From registration to the first of either disease progression or death from any cause, assessed up to 5 years
Safety Issue:
Description:Progression-free survival is defined as the time from registration to clinical or radiographic disease progression or death, whichever occurs first, as defined by RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported.
Measure:Overall survival
Time Frame:From registration to death from any cause, assessed up to 5 years
Safety Issue:
Description:Overall survival (OS) is defined as the time from registration to death from any cause. OS will be estimated using the Kaplan-Meier method. The median overall survival and corresponding 95% confidence interval will be reported.
Measure:Duration of response
Time Frame:From first documentation of an objective response to the earliest date disease progression is documented or death from any cause, assessed up to 5 years
Safety Issue:
Description:Duration of response is defined as the duration of time from first documentation of an objective response to the earliest date disease progression is documented or death from any cause. Duration of response will be estimated using the Kaplan-Meier method. The median duration of response and corresponding 95% confidence interval will be reported.
Measure:Time to response
Time Frame:From registration to the first documentation of an objective response, assessed up to 5 years
Safety Issue:
Description:Time to response is defined as the duration of time from registration to the first documentation of an objective response. Time to response will be estimated using the Kaplan-Meier method. The median time to response and corresponding 95% confidence interval will be reported.
Measure:Incidence of adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Adverse Events as defined by National Institute of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All patients who have initiated treatment will be considered evaluable for adverse event analyses. The rate of patients experiencing a grade 3+ adverse event will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Academic and Community Cancer Research United

Last Updated

May 18, 2020