Combination Therapy in Cancers With Mutations in DNA Repair Genes
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.
Timeline
- Start
- 2023-05-23
- Primary completion
- 2028-01-31
- Completion
- 2028-01-31
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Irinotecan | Small molecule | 100 mg/m2 | Intravenous |
| Subject | Irinotecan | Small molecule | 150 mg/m2 | Intravenous |
| Subject | Niraparib | Small molecule | 100 mg | Oral |
| Subject | Niraparib | Small molecule | 200 mg | Oral |
| Subject | Niraparib | Small molecule | 300 mg | Oral |