Combination Therapy in Cancers With Mutations in DNA Repair Genes

Part of paid clinical trials in San Francisco, California.

Sponsor
University of California, San Francisco
Study ID
NCT05694715
Phase
PHASE1
Status
Recruiting
Apply to this trial

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
May 23, 2023
Status verified
Mar 2026
Primary completion
Jan 31, 2028
Completion
Jan 31, 2028

Study Design

Enrollment
24 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1 (Niraparib, Irinotecan)
    Participants will receive a starting dose of 100 mg of niraparib on days 1-7 each 21-day cycle, and 100 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.
  • Experimental: Cohort 2 (Niraparib, Irinotecan)
    Participants will receive a starting dose of 200 mg of niraparib on days 1-7 each 21-day cycle, and 100 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.
  • Experimental: Cohort 3a (Niraparib, Irinotecan)
    Participants weighing \< 77 kg will receive a starting dose of 200 mg of niraparib on days 1-7 each 21-day cycle, and 100 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.
  • Experimental: Cohort 3b (Niraparib, Irinotecan)
    Participants weighing \>= 77 kg will receive a starting dose of 300 mg of niraparib on days 1-7 each 21-day cycle, and 100 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.
  • Experimental: Cohort 4a (Niraparib, Irinotecan)
    Participants weighing \< 77 kg will receive a starting dose of 200 mg of niraparib on days 1-7 each 21-day cycle, and 150 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.
  • Experimental: Cohort 4b (Niraparib, Irinotecan)
    Participants weighing \>= 77 kg will receive a starting dose of 300 mg of niraparib on days 1-7 each 21-day cycle, and 150 mg/m\^2 of irinotecan on day 1 of each 21 day cycle until unacceptable toxicity, disease progression or participant withdrawal.

Primary Outcome Measure

Percentage of participants with treatment-emergent adverse events [ Time Frame: 30 days after the last dose ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of California, San FranciscoSan FranciscoCalifornia94143
Early Phase Clinical Trials Recruitment
[email protected]
877-827-3222
[email protected]
Pamela Munster, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in San Francisco, CA

By research site
University of California, San Francisco· San Francisco, CA

Related Studies