Binimetinib and Hydroxychloroquine in Treating Patients With KRAS Mutant Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This phase I trial studies the best dose of hydroxychloroquine when given together with binimetinib in treating patients with KRAS gene mutated pancreatic cancer that has spread to other places in the body (metastatic). Binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hydroxychloroquine may prevent autophagy, a normal process in which a cell destroys proteins and other substances which may lead to cell death. Autophagy may prevent normal cells from developing into tumor cells, but it may also protect tumor cells by destroying anticancer drugs or substances taken up by them. Giving hydroxychloroquine together with binimetinib may work better in treating patients with pancreatic cancer compared to binimetinib alone.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose of hydroxychloroquine (HCQ) when combined with a fixed dose of binimetinib. SECONDARY OBJECTIVES: I. To determine the response rate among a pilot cohort of pancreatic cancer patients. II. To determine the safety and toxicity profile of the combination of binimetinib and HCQ. III. To determine the ability of the combination to halt tumor growth as measured by progression free survival. IV. To assess the overall survival of patients treated on this regimen. EXPLORATORY OBJECTIVES: I. To compare the efficacy of treatment to somatic gene mutation profile as acquired by standard of care testing. II. To assess pre- and post- treatment tissue to determine if markers of autophagy correlate with response to treatment. III. To assess the effect of this binimetinib/HCQ treatment on changes in muscle and fat mass as analyzed by computed tomography (CT) scan (as standard of care treatment). OUTLINE: This is a dose-escalation study of hydroxychloroquine. Patients receive binimetinib orally (PO) twice daily (BID) and hydroxychloroquine PO BID on days 1-14. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 30 days.

Intervention public domain (ClinicalTrials.gov)

Drug: Binimetinib. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Hydroxychloroquine. Given PO

Arm public domain (ClinicalTrials.gov)

Treatment (binimetinib, hydroxychloroquine) (experimental): Patients receive binimetinib PO BID and hydroxychloroquine PO BID on days 1-14. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Primary outcome public domain (ClinicalTrials.gov)

Maximum tolerated dose (MTD). Will employ the Bayesian optimal interval (BOIN) design to find the MTD. Time frame: Up to 30 days.

Secondary outcome public domain (ClinicalTrials.gov)

Response rate. Time frame: Up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Incidence of adverse events. Time frame: Up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Progression free survival. Time frame: Up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival. Time frame: Up to 1 year.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report with radiologically identified metastases that meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria. * Be willing and able to provide written informed consent for the trial. * Have at least one measurable lesion by RECIST criteria. * Have had prior treatment with at least one line of therapy for metastatic disease. * Have had tumor mutation profiling from any Clinical Laboratory Improvement Act (CLIA) certified laboratory demonstrating a KRAS mutation. Liquid biopsy demonstrating KRAS mutation will be considered acceptable. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale. * Absolute neutrophil count (ANC) \>= 1500/uL (specimens must be collected within 10 days prior to the start of trial treatment). * Platelets \>= 100,000/uL (specimens must be collected within 10 days prior to the start of trial treatment). * Hemoglobin \>= 9.0 g/dL (specimens must be collected within 10 days prior to the start of trial treatment). * Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 x upper limit of normal (ULN) OR \>= 50 mL/min for subjects with creatinine level \> 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment). * Total bilirubin =\< 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment). * Indirect bilirubin =\< ULN (specimens must be collected within 10 days prior to the start of trial treatment). * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment). * Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment). * Serum albumin \> 3.3 mg/dl (specimens must be collected within 10 days prior to the start of trial treatment). * International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 34 participants (actual).