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New treatment option for BRCA1 Mutation
Official title Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors
ClinicalTrials.gov ID: NCT06177171
What this study is testing
What is Olaparib?
Olaparib is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for brca1 mutation.
Also referred to as LYNPARZA.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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).
- Phase 1: an early, usually small safety study
- Time commitment: about 2 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with: Phase I, Dose Escalation...
- Expansion Cohort A (n=6): Germline mutation\ (with or without accompanying somatic mutation) in one or more of the following genes: BRCA1, BRCA2...
- 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.
- Testing for DNA repair mutations should occur prior to study consent or enrollment via a CLIA-approved test.
- Has measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in previously irradiated areas are considered measurable if...
You likely can't join if
- Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant...
- 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...
- Individuals who are pregnant (because of the potential for olaparib and ASTX727 to cause serious adverse reactions to the unborn child). Females of...
See the full eligibility criteria
Who can join
- Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with: Phase I, Dose Escalation: Germline and/or somatic mutation\ in one or more of the following genes...
- 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.
- Testing for DNA repair mutations should occur prior to study consent or enrollment via a CLIA-approved test.
- 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.
- 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.
- Age \>=18 years
- Eastern Cooperative Oncology Group (ECOG) performance status \ 60%
- Demonstrates adequate organ function as defined below: Adequate bone marrow function:
- hemoglobin \>=10.0 g/dl
- absolute neutrophil count \>=1,500/microliter (mcL)
- platelets \>=100,000/mcL Adequate hepatic function:
- total bilirubin ≤ 1.5 x institutional upper limit normal (ULN)
- aspartate aminotransferase (AST)/(SGOT) \<= 2.5 x institutional ULN
- alanine aminotransferase (ALT)/(SGPT) \<= 2.5 x institutional ULN
- creatinine \ = 50 mL/min/1.73 m\^2, calculated using the Cockcroft-Gault equation.
- Ability to understand and the willingness to sign a written informed consent document.
- Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. Individuals with HCV infection who are currently on treatment could be eligible if HCV viral load is undetectable.
- Individuals with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 4 weeks. Participants need to be...
- Based on findings from human data and/or animal studies, and their mechanisms of action, ASTX727 and olaparib can cause fetal harm when administered to a pregnant woman. For this reason, females of child-bearing...
- Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible...
What rules you out
- 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...
- 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...
- 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...
- Diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Taking a prohibited medication that cannot be safely discontinued or substituted.
The study team makes the final eligibility decision.
Where it's taking place
- San Francisco, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include San Francisco, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.