Combination Therapy in Cancers With Mutations in DNA Repair Genes

This is an open label, non-randomized phase Ib dose finding study of niraparib and irinotecan combination therapy. For this study, individuals with metastatic solid tumor malignancies and BRCA1/2, ataxia telangiectasia mutated gene (ATM), or PALB2 mutations will be enrolled with specific tumors of interest including gastrointestinal cancers (e.g. colon, pancreas, gastric, cholangiocarcinoma), ovarian cancer, and breast cancer. PRIMARY OBJECTIVES: I. To assess safety and tolerability of niraparib and irinotecan combination therapy in patients with metastatic solid tumor malignancies and BRCA1/2, ATM, or PALB2 mutations. II. To determine the MTD and recommended phase II dose of niraparib with irinotecan combination therapy. SECONDARY OBJECTIVES: I. To determine the preliminary efficacy of niraparib and irinotecan combination therapy in patients with metastatic solid tumor malignancies and BRCA1/2, ATM, or PALB2 mutations. OVERVIEW: Participants will be treated in cohorts of size three to six, and the dosage will be escalated if the clinical toxicity is acceptable. Participants may continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, start of new anti-cancer therapy, or death. Participants will be followed for 30 days after study drug discontinuation for safety and every 12 weeks (+/- 2 weeks) for up to 2 years after start of therapy until disease progression or death from any cause (whichever occurs first).