Combination Therapy in Cancers With Mutations in DNA Repair Genes
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Francisco
About this trial
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.
Eligibility criteria
Qualifiers
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.
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
Disqualifiers
Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study at clinician's discretion and not otherwise stated below.
Prior allergic reaction to PARP inhibitor or irinotecan or their excipients. Prior PARP inhibitor or irinotecan (or topoisomerase 1 inhibitors) use is allowed.
Individuals with known toxicity to irinotecan (e.g., grade 3 or 4 neutropenia) or suspected sensitivity.
Individuals with homozygous or compound heterozygous UGT1A1 polymorphisms (e.g., alleles *28/*28, *6/*6, or *6/*28) predicted to be associated with medium-to-high risk of irinotecan-related toxicity
Trial design
Treatments tested in this trial
- Niraparib
- Irinotecan
Treatment groups
24 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Sponsors and collaborators
University of California, San Francisco
Lead sponsor
GlaxoSmithKline
Collaborator
Source ClinicalTrials.gov