This is a phase 2 study to test the effectiveness (anti-tumor activity) of the combination of the study drugs, Senaparib and Temozolomide, in patients with clear cell or endometrioid ovarian cancers that have ARID1A pathologic variants.
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Pathologically (histologically or cytologically) confirmed diagnosis of recurrent or persistent clear cell or endometrioid ovarian, fallopian tube, or primary peritoneal carcinoma. Histologic documentation (via the pathology report) indicating at least 50% endometrioid or clear cell morphology is required.
Presence of an ARID1A pathologic variant or likely pathogenic variant identified by next generation sequencing (NGS) tests (per criteria below)
Pathogenic or likely pathogenic ARID1A variant identified NGS tests performed by the labs listed on https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed for the purposes of this study.
Prior treatment with a poly ADP ribose polymerase (PARP) inhibitor or temozolomide.
Patients who are currently receiving or have previously received any other investigational agents within 3 weeks prior to entering the study.
Patients who have not recovered (CTCAE v5 grade ≤1) from adverse events due to agents administered more than 4 weeks earlier, unless those events are deemed to have returned to baseline, are irreversible, or are unlikely to develop into a life-threatening condition at the permission of the Protocol Chair (e.g., alopecia).
A prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
Single group
Senaparib
DrugParticipants will receive orally 80mg daily Days 1-28 of a 28 day cycle.
Temozolomide
DrugParticipants will receive orally 20mg daily Days 1-21 of a 28 day cycle.
Objective Response Rate (ORR)
Clinical activity (response frequency) of Senaparib and Temozolomide. The primary endpoint of clinical activity is the objective response rate (ORR) defined as complete response (CR) + partial response (PR). Tumor response is defined by RECIST v 1.1. If a patient fails to respond (or has stable disease), the patient will be defined as a non-responder in the analysis. ORR will be estimated using binomial distribution together with 95% Clopper-Pearson confidence interval.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Examine the nature and degree of toxicity in patients treated with this regimen. Safety and tolerability will be assessed by clinical review of all relevant parameters including adverse events (AEs), serious AEs (SAEs). Frequency and severity (grades based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 of AEs will be summarized by system organ class, preferred term, and relation to study drug.
Frequency of Grade 3 and 4 Adverse Events
Number of Grade 3 and 4 treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria will be summarized.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Impact Therapeutics
Collaborator
