Combination Therapy in Cancers With Mutations in DNA Repair Genes (NCT05694715) | Clinical Trial Compass
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 range
18 Years
Sex
ALL
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
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Percentage of participants with treatment-emergent adverse events
Timeframe: 30 days after the last dose
2
Maximum Tolerated Dose (MTD)
Timeframe: 30 days after the last dose
3
Percentage of participants with Dose Limiting Toxicities (DLTs)
. 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
. 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
. Individuals receiving any other investigational agents concurrently with the study drugs within 3 weeks or 5 half-lives, whichever is shorter, of the first dose of therapy preceding the study.
. Participants with unstable brain metastases are excluded. Patients with a history of brain metastases (\>1cm) are permitted to enroll if they have been treated and have been stable for a minimum of one month on imaging. Patients may not currently receive steroids for their brain metastases. Patients with small, asymptomatic brain metastases (\<1cm) may enroll.
. Individuals with a second primary malignancy
. Individuals with a prior history of posterior reversible encephalopathy syndrome (PRES)