Actively Recruiting
Combination Therapy in Cancers With Mutations in DNA Repair Genes
Led by University of California, San Francisco · Updated on 2026-03-17
24
Participants Needed
1
Research Sites
244 weeks
Total Duration
On this page
Sponsors
U
University of California, San Francisco
Lead Sponsor
G
GlaxoSmithKline
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Combination Therapy in Cancers With Mutations in DNA Repair Genes
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Individuals 18 years of age or older
- Ability to understand and sign informed consent and follow study procedures
- Solid tumors responsive to topoisomerase I inhibitors, including gastrointestinal, breast, and ovarian cancers, with BRCA1, BRCA2, ATM, or PALB2 mutations confirmed by approved testing
- At least one measurable tumor lesion by RECIST 1.1 criteria
- Advanced solid tumors without curative treatment options
- At least 3 weeks or 5 half-lives since last anticancer therapy, with recovery from toxicities to less than grade 2
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function based on blood counts and liver, kidney tests
- Recovery from prior treatment toxicities to less than grade 2, except some mild chronic side effects
- Ability to take oral medications
- Use of highly effective contraception during treatment and for specified periods after treatment for those of reproductive potential
- HIV-positive individuals on effective treatment with undetectable viral load within 6 months allowed
- Controlled chronic hepatitis B or treated hepatitis C infection with undetectable viral load
You will not qualify if you...
- Any significant medical condition or lab abnormalities posing unacceptable risk
- Allergic reaction to PARP inhibitors or irinotecan
- Known severe toxicity or sensitivity to irinotecan
- High-risk UGT1A1 polymorphisms increasing irinotecan toxicity risk
- Use of other investigational agents within 3 weeks before study start
- Unstable brain metastases or current steroid treatment for brain metastases
- Presence of a second primary cancer
- History of posterior reversible encephalopathy syndrome (PRES)
- Uncontrolled high blood pressure
- Malabsorption syndromes or uncontrolled nausea, vomiting, or diarrhea
- Diagnosis of myelodysplastic syndromes or acute myeloid leukemia
- Known Gilbert's disease
- Pregnancy or breastfeeding, or planning pregnancy during and shortly after treatment
- Inability or unwillingness to comply with study procedures or contraception requirements
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
Research Team
E
Early Phase Cancer Clinical Trials Recruitment
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
6
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