RecruitingPhase 1

Combination Therapy in Cancers With Mutations in DNA Repair Genes

United States24 participantsStarted 2023-05-23

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Individuals 18 years of age or older.
✓. 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.
✓. 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 defects:
✓. Presence of at least one lesion with measurable disease as defined by RECIST 1.1 criteria for response assessment
✓. Advanced solid tumor malignancy without curative options
✓. At least 5 half-lives or 3 weeks (whichever is shorter) must have passed since last anticancer therapy
✓. The washout period for investigational agents without published half-lives should be 3 weeks since last therapy, and all treatment related toxicities must have recovered to less than grade 2.
✓. Eastern Cooperative Oncology Group (ECOG) Performance Status of \<=1 (Karnofsky \> 60%; Appendix 1).

Exclusion criteria

What they're measuring

Percentage of participants with treatment-emergent adverse events

Timeframe: 30 days after the last dose

Maximum Tolerated Dose (MTD)

Timeframe: 30 days after the last dose

Percentage of participants with Dose Limiting Toxicities (DLTs)

Timeframe: 30 days after the last dose

Recommended Phase 2 Dose (RP2D)

Timeframe: Up to 2 years

Trial details

NCT IDNCT05694715

SponsorUniversity of California, San Francisco

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-01-31

Contact for this trial

Early Phase Cancer Clinical Trials Recruitment

877-827-3222 EarlyPhaseClinicalTrials@ucsf.edu

View on ClinicalTrials.gov More Metastatic Solid Tumor trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Individuals 18 years of age or older.
✓. 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.
✓. 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 defects:
✓. Presence of at least one lesion with measurable disease as defined by RECIST 1.1 criteria for response assessment
✓. Advanced solid tumor malignancy without curative options
✓. At least 5 half-lives or 3 weeks (whichever is shorter) must have passed since last anticancer therapy
✓. The washout period for investigational agents without published half-lives should be 3 weeks since last therapy, and all treatment related toxicities must have recovered to less than grade 2.
✓. Eastern Cooperative Oncology Group (ECOG) Performance Status of \<=1 (Karnofsky \> 60%; Appendix 1).

Exclusion criteria

What they're measuring

Percentage of participants with treatment-emergent adverse events

Timeframe: 30 days after the last dose

Maximum Tolerated Dose (MTD)

Timeframe: 30 days after the last dose

Percentage of participants with Dose Limiting Toxicities (DLTs)

Timeframe: 30 days after the last dose

Recommended Phase 2 Dose (RP2D)

Timeframe: Up to 2 years