Advanced Malignant Solid Neoplasm Clinical Trial
Official title:
Phase II Open-Label Multi-Cohort Study Evaluating CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Patients With Advanced Chemorefractory Colorectal, Pancreatic, or Other Solid Cancers
This phase II trial tests how well CPI-613 (devimistat) in combination with hydroxychloroquine (HCQ) and 5-fluorouracil (5-FU) or gemcitabine works in patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that have not responded to chemotherapy medications (chemorefractory). Metabolism is how the cells in the body use molecules (carbohydrates, fats, and proteins) from food to get the energy they need to grow, reproduce and stay healthy. Tumor cells, however, do this process differently as they use more molecules (glucose, a type of carbohydrate) to make the energy they need to grow and spread. CPI-613 works by blocking the creation of the energy that tumor cells need to survive, grow in the body and make more tumor cells. When the energy production they need is blocked, the tumor cells can no longer survive. Hydroxychloroquine is a drug used to treat malaria and rheumatoid arthritis and may also improve the immune system in a way that tumors may be better controlled. Fluorouracil is in a class of medications called antimetabolites. It works by killing fast-growing abnormal cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. CPI-613 (devimistat) in combination with hydroxychloroquine and 5-fluorouracil or gemcitabine may work to better treat advanced solid tumors.
PRIMARY OBJECTIVE: I. The primary objective of this study will be to estimate the overall response rate (ORR) of treatment with devimistat (CPI-613) plus HCQ and, depending on the cohort and indication, either 5-FU or gemcitabine. SECONDARY OBJECTIVES: I. Evaluate progression-free survival (PFS) of patients with solid tumors that are treated with CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or gemcitabine. II. Determine overall survival (OS) of patients with solid tumors that are treated with CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or gemcitabine. III. Assess duration of response (DOR) of patients with solid tumors that are treated with CPI-613 plus HCQ and, depending on the cohort and indication, either 5-FU or gemcitabine. IV. Assess safety and tolerability for patients with solid tumors treated with specified treatments. EXPLORATORY OBJECTIVES: I. Blood from patients in cohort 3 that consent will be collected at baseline, cycle 1, day 1 (C1D1), C1D15, C2D1, and at the time of treatment discontinuation for further molecular and metabolic analysis, possibly including but not limited to proteomic, metabolomic, and genetic/genomic analysis. OUTLINE: Patients are assigned to 1 of 3 cohorts. COHORT 1: Patients with colorectal cancer receive devimistat intravenously (IV), 5-FU IV, plus HCQ orally (PO) on study. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) and undergo blood specimen collection throughout the study. COHORT 2: Patients with pancreatic cancer receive devimistat IV, 5-FU IV, plus HCQ PO on study. Patients also undergo CT and/or MRI and undergo blood specimen collection throughout the study. COHORT 3: Patients with gastroesophageal cancer receive devimistat IV, 5-FU IV, plus HCQ PO on study. Patients with urothelial, ovarian, or non-small cell lung cancer receive devimistat IV, gemcitabine IV, plus HCQ PO on study. Patients with biliary tumors receive devimistat IV and gemcitabine IV or HCQ PO on study. Patients also undergo CT and/or MRI and undergo blood specimen collection throughout the study. ;
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