NCT05694715

Combination Therapy in Cancers With Mutations in DNA Repair Genes

Combination Therapy of Niraparib and Irinotecan in Cancers With Mutations in DNA Repair Genes

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 BRCA1/2, 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).

Conditions

• Metastatic Solid Tumor
• BRCA1 Mutation
• BRCA2 Mutation
• ATM Gene Mutation
• PALB2 Gene Mutation

Interventions

Type	Name	Description
DRUG	Niraparib	Given orally
DRUG	Irinotecan	Given intravenously (IV)

Timeline

• Start date: 2023-05-23
• Primary completion: 2028-01-31
• Completion: 2028-01-31
• First posted: 2023-01-23
• Last updated: 2026-03-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study