Study of Senaparib in Combination With Temozolomide in ARID1A Mutation Associated Ovarian Cancer

NCT06617923 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: J2467sIRBIRB00443678
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Ovary Cancer; Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer

Keywords

ovarian; endometrioid; clear cell; ARID1A mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  3 years

• Frequency of Grade 3 and 4 Adverse Events

  3 years

Study Arms (1)

Treatment

EXPERIMENTAL

Senaparib 80mg Temozolomide 20mg

Drug: Senaparib; Drug: Temozolomide

Interventions

Senaparib DRUG

Participants will receive orally 80mg daily Days 1-28 of a 28 day cycle.

Treatment

Temozolomide DRUG

Participants will receive orally 20mg daily Days 1-21 of a 28 day cycle.

Also known as: TMZ

Treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women with clear cell or endometrioid ovarian, fallopian tube, or primary peritoneal cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Pathogenic ARID1A mutation identified by other NGS tests will need to be confirmed by the study PI prior to enrollment.
• All patients must have measurable disease, according to RECIST v1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. To be considered pathologically enlarged and measurable, a lymph node must be ≥15 mm in short axis when assessed by CT scan or MRI (CT scan slice thickness recommended to be no greater than 5 mm). See Section 12 for the evaluation of measurable disease.
• Patients who have received radiation must have evidence of measurable disease outside of the radiation field or have documented progression after radiation at the time of enrollment.
• Patients must have received at least two prior cytotoxic regimens or have platinum-resistant (defined as having progressed within 6 months of last platinum therapy) or platinum-refractory (having progressed during primary platinum therapy) disease.
• Participants can have received no more than 3 prior lines of cytotoxic therapy (any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow).
• Unlimited prior hormonal therapy, targeted therapy (including immunotherapy) or antiangiogenic therapy will be permitted.
• Patients must have completed prior therapy as detailed below:
• Prior Therapy Time from last prior therapy to study treatment start date Chemotherapy (except nitrosoureas or mitomycin C) ≥ 28 days; Nitrosoureas or mitomycin C ≥ 42 days; Small molecule inhibitors ≥ 28 days; Monoclonal antibodies ≥ 28 days; Immunotherapy ≥ 28 days; Radiotherapy (RT) ≥ 28 days from last local site RT ≥ 28 days from stereotactic radiosurgery; ≥ 12 weeks from craniospinal ≥50% radiation of pelvis or total body irradiation Radiation related side effects must have resolved prior to study enrollment Endocrine therapy ≥ 7 days
• Ability to take oral medications and not have gastrointestinal illnesses that would preclude absorption of senaparib or TMZ as judged by the treating physician.
• Patients assigned female at birth, age ≥18 years. Because no dosing or adverse event data are currently available on the use of senaparib and TMZ in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%, see Appendix A).

You may not qualify if:

• 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).
• Patients who have any of the following:
• A prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
• Abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
• A prior history of T-cell lymphoblastic lymphoma/lymphoblastic leukemia (T-ALL).
• Patients with clinical or radiographic evidence of bowel obstruction.
• Severe, active comorbidity per the treating investigator's clinical discretion.
• Pregnant or lactating patients.
• Patients with known human immunodeficiency virus (HIV) infection are ineligible because the treatments involved in this protocol may be immunosuppressive, increasing the risk of lethal infections in this patient population.
• Patients with known, untreated brain metastases, as progressive neurologic dysfunction may develop that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to senaparib or temozolomide.
• Strong CYP3A4 inhibitors or inducers should not be used within 3 days of Day 1 dosing until the end of study. Moderate CYP3A4 inhibitors or inducers should be used with caution.
• Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list such as http://medicine.iupui.edu/ clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• Impact Therapeutics: collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

RECRUITING

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

senaparib; Temozolomide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Stephanie Gaillard, MD PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hopkins GYN Trials

CONTACT

410-614-1361; HopkinsGynTrials@jhmi.edu

Sidney Kimmel Cancer Center Clinical Research Office

CONTACT

410-955-8866; jhcccro@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: two-stage, non-randomized

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: October 1, 2024
• Study Start: February 6, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 27, 2025

Record last verified: 2025-10

Locations

US (2)