Combination Therapy of Niraparib and Irinotecan in Cancers With Mutations in DNA Repair Genes
University of California, San Francisco
Summary
The purpose of this phase 1 clinical trials is to determine whether niraparib (a Poly (ADP-ribose) polymerase inhibitor (PARPi)) can be safely combined with irinotecan with manageable toxicity and reasonable efficacy. Emerging evidence suggest that PARPi is an effective therapeutic strategy in a wider subset of solid tumors that may have defective homologous recombination (HR) or DNA repair gene mutations. BReast CAncer gene (BRCA), partner and localizer of BRCA2 (PALB2), and various other DNA repair germline mutations predispose carriers to cancers of the breast, ovaries, pancreas, prostate and melanoma. A number of preclinical studies have demonstrated that PARP inhibitors can work as chemopotentiators. There is significant interest in this combination, and the recommended phase II dose will be used in the upcoming NCI ComboMatch trial.
Description
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Individuals 18 years of age or older. 2. Ability to understand and willingness to voluntarily sign a written informed consent document prior to any study-related assessments or procedures are conducted; and willing and able to adhere to the study visit schedule and other protocol requirements. 3. Solid tumors where topoisomerase I inhibitors have shown efficacy, including gastrointestinal tumors (e.g., colon, pancreatic, gastric cancer and cholangiocarcinoma), breast cancer, and ovarian cancer (prostate cancer is excluded), with one or more of the following DNA repair d…
Interventions
- DrugNiraparib
Given orally
- DrugIrinotecan
Given intravenously (IV)
Location
- University of California, San FranciscoSan Francisco, California