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DNMT Inhibitor

Olaparib + ASTX727 for BRCA Mutations

Phase 1

Recruiting

Led By Pamela Munster, MD

Research Sponsored by Pamela Munster

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with specific genetic mutations

For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

Must not have

Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks

Has not recovered from adverse events due to prior anti-cancer therapy to <= grade 1 (CTCAE v5.0) or baseline (other than alopecia)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, olaparib and ASTX727, in adults with advanced or metastatic solid tumors. The patients in this trial have specific gene mutations related to

Who is the study for?

Adults with advanced or metastatic solid tumors that have specific genetic mutations in the HRR pathway, such as BRCA1, BRCA2, PALB2, ATM, and CHEK2. Participants must have a mutation related to their cancer.

What is being tested?

The trial is testing a combination of two drugs: Olaparib (a PARP inhibitor) and ASTX727 (an oral drug combining decitabine with cedazuridine). It's designed to see how well these drugs work together against certain tumor mutations.

What are the potential side effects?

Possible side effects include nausea, fatigue, low blood cell counts leading to increased infection risk or bleeding problems, digestive issues like constipation or diarrhea, and potential liver function changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My advanced cancer has specific genetic mutations.

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My hepatitis B is under control with treatment.

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I am 18 years old or older.

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I had hepatitis C but have been successfully treated and cured.

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I am mostly self-sufficient and can carry out daily activities.

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I am HIV-positive, on treatment, and my viral load has been undetectable for 6 months.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had cancer treatments or radiation in the last 3 weeks, or antibody therapy in the last 4 weeks.

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I have recovered from previous cancer treatment side effects, except for hair loss.

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I cannot swallow pills.

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I have been diagnosed with MDS or AML.

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I am on medication that cannot be stopped or changed for the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD) (Phase 1 Only)

Percentages of dose-limiting toxicities (DLTs) (Phase 1 Only)

Proportion of participants with treatment-emergent Adverse Events (AEs) (Phase 1 Only)

+1 more

Secondary study objectives

Median Duration of Stable Disease (SD) (Phase 2 only)

Median Duration of overall Response (DoR) (Phase 2 only)

Median Progression-Free Survival (PFS) (Phase 2 only)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 1b: RP2D (Olaparib, ASTX727) - Dose ExpansionExperimental Treatment2 Interventions

Participants enrolled in this cohort will receive the RP2D based on the safety and efficacy profile determined in the Phase 1 cohorts. Participants will receive the RP2D dose of olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 at the RP2D for the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first.

Group II: Phase 1: Olaparib, ASTX727 (D1,D3)-Starting DoseExperimental Treatment2 Interventions

Participants enrolled in the starting dose cohort will receive 300 mg Olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 on days 1, and 3 of the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first. If no DLTs are reported for the first 3 participants, an additional dose escalation cohort may open at the next dose level.

Group III: Phase 1: Olaparib + ASTX727 (D1,D3,D5)Experimental Treatment2 Interventions

If no DLTs are reported in the previous dose level, participants enrolled in this cohort will receive 300 mg olaparib orally, twice a day (BID) on day 1 and day 14 for each 28-day cycle. Participants will also receive 35/100mg ASTX727 on days 1, 3 and 5 of the 28-day cycle. Participants may continue study treatment indefinitely until disease progression unacceptable toxicity, withdrawal, or study closure; whichever comes first.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ASTX727

2018

Completed Phase 3

~270

Olaparib

2007

Completed Phase 4

~2190