Phase 1 Study of Niraparib and Irinotecan Combination Therapy in Metastatic Solid Tumors With DNA Repair Gene Mutations Including BRCA12, ATM, and PALB2

What this Trial Is About

Researchers are evaluating the combination of niraparib, a PARP inhibitor, with irinotecan in patients who have metastatic solid tumors and mutations in DNA repair genes such as BRCA12, ATM, or PALB2. This phase 1 trial aims to assess whether this combination can be given safely with manageable side effects and to determine the best dose for future studies. The study focuses on cancers like gastrointestinal tumors, ovarian cancer, and breast cancer where DNA repair defects are present. Participants will receive niraparib orally for the first 7 days of each 21-day cycle and irinotecan intravenously on day 1 of each cycle. Dosages of niraparib vary based on participant weight, ranging from 100 mg to 300 mg, while irinotecan doses are either 100 mgm or 150 mgm. Treatment continues until unacceptable side effects, disease progression, withdrawal, new cancer therapy, or death. Dose escalation is done in small groups to find the maximum tolerated dose. During the study, participants will be monitored for side effects for 30 days after stopping treatment and followed every 12 weeks for up to 2 years or until disease progression or death. Researchers will assess treatment safety, dose-limiting toxicities, response rates, duration of response, and progression-free survival. The total study duration includes active treatment and extended follow-up to evaluate both safety and preliminary effectiveness.

Combination Therapy in Cancers With Mutations in DNA Repair Genes