Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors (NCT06177171) | Clinical Trial Compass
RecruitingPhase 1
Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors
United States18 participantsStarted 2024-02-07
Plain-language summary
This is a single center, phase I/Ib clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced/metastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and/or Checkpoint kinase 2 (CHEK2) mutations).
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
. Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with:
. Expansion Cohort A (n=6): Germline mutation\* (with or without accompanying somatic mutation) in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2;
. Expansion Cohort B (n=6): Germline and/or somatic mutation\* in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2.
. Has measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions.
. Participants may have received any lines of prior therapy and is refractory or intolerant to therapy approved for their condition or unwilling to receive currently approved 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
Proportion of participants with treatment-emergent Adverse Events (AEs) (Phase 1 Only)
Timeframe: Up to 2 years
2
Percentages of dose-limiting toxicities (DLTs) (Phase 1 Only)
. Prior PARP inhibitors are allowed, provided the following two criteria are met:
. Participant has NOT required toxicity related dose reductions or dose delays during prior PARP inhibitor treatment; and
. Participant has NOT experienced any allergic reaction to PARP inhibitors.
Exclusion criteria
. Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of Luteinizing hormone-releasing hormone (LHRH) analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.
. Has not recovered from adverse events due to prior anti-cancer therapy to \<= grade 1 (CTCAE v5.0) or baseline (other than alopecia).
. Receipt of any other investigational agents or devices within 3 weeks prior to initiation of trial therapy.
. Unable to swallow oral medications
. Individuals who are breast-feeding/chest-feeding (because of the potential for serious adverse reactions in breastfeed infants from olaparib and ASTX727). Study participants who are lactating must agree to discontinue breast-feeding/chest-feeding for the duration of study treatment and for 1 month after the final dose of trial therapy.
. Individuals who are pregnant (because of the potential for olaparib and ASTX727 to cause serious adverse reactions to the unborn child). Females of childbearing potential (defined below) must have a negative urine or serum pregnancy test within 72 hours prior to first administration of study drug. A female is considered to be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), unless it is documented that the individual meets either of the following two criteria: (1) has reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries). Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study activities, interfere with participant safety, or study endpoints.
. Diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
. Taking a prohibited medication that cannot be safely discontinued or substituted.