A Study Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in Participants With Homologous Recombination-Deficient Stage III/IV Ovarian Cancer (COHORT-C)

Phase 2

Terminated

Conditions: Ovarian Neoplasms

Interventions: Drug: Niraparib
Drug: Carboplatin
Drug: Paclitaxel

Registration Number: NCT06964165

Lead Sponsor: Tesaro, Inc.

Brief Summary: The goal of the study is to learn whether Niraparib or Platinum-Taxane Doublet chemotherapy is better in treating participants with Homologous Recombination Deficient (HRd) Stage III/IV Ovarian Cancer (OC). This study is a sub-study of the Master protocol -OPAL (NCT03574779)

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 36

Inclusion Criteria

Participant has newly diagnosed Stage III or IV ovarian, fallopian tube, or primary peritoneal cancer according to the International Federation of Gynecology and Obstetrics staging criteria.
Participants must provide sufficient tumor tissue at Prescreening and agree to undergo a central HRD tumor testing using a fully validated assay. The participants must be HRd as per central HRD tumor testing result for eligibility.
1. Participants with a documented germline breast cancer susceptibility gene (BRCA) 1/2 deleterious or suspected deleterious mutations by Sponsor's permitted test (e.g., BRACAnalysis CDx) may be allowed to enroll prior to receiving the central test results, provided all inclusion criteria are met. However, tumor sample submitted by these participants will still be required for central HRD confirmation. The list of Sponsor's permitted tests will be provided by the Sponsor.
2. All participants must agree to provide tumor tissue collected from IDS.
3. Participant must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides if blocks are not available) with sufficient tumor content (as confirmed by the Sponsor's designated central and/or testing laboratory) for central HRD testing at Prescreening and for exploratory biomarker testing at Prescreening or Screening. If sufficient tumor tissue is provided at Prescreening, participants do not need to provide additional tissue at Screening.
Participant must have completed 1 run-in cycle of carboplatin-paclitaxel and not experienced disease progression after this treatment. Completion is defined as receiving ≥50% of the prescribed dose of therapy within 5 weeks.
Participant must not have known contraindication or uncontrolled hypersensitivity to carboplatin and paclitaxel and their excipients and no known pre-existing conditions that would preclude treatment with these agents.
Participant must not have known contraindication or uncontrolled hypersensitivity to niraparib and its excipients.
Participant must not have symptomatic ascites or pleural effusions as defined by the following criterion: presence of fluid in the abdominal or pleural cavities requiring removal within 1 week prior to signing the informed consent.
Participant must agree to complete Patient-reported outcome (PRO) and work productivity questionnaires throughout the study.

Exclusion Criteria

Participant has low-grade or Grade 1 epithelial Ovarian Cancer (OC) or mucinous, germ cell, transitional cell, carcinosarcoma, or undifferentiated tumor.
Participant has contraindications to surgery.
Participant has a bowel obstruction by clinical symptoms or Computed tomography (CT) scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
Participant has any known history or current diagnosis of Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).
Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to the start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known Human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
1. Cluster of differentiation 4-positive T cell count ≥350/μL and viral load <400 copies/mL
2. No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months prior to enrollment
3. No history of HIV-associated malignancy for the past 5 years
4. Concurrent antiretroviral therapy as per the most current National Institutes of Health Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study enrollment
Participant received prior treatment for high-grade non-mucinous epithelial ovarian, fallopian tube, or peritoneal cancer (e.g., prior surgery, immunotherapy, anticancer therapy [with the exception of 1 run-in cycle of carboplatin-paclitaxel], or radiation therapy).
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone or insulin).
Participant is unable to swallow orally administered medication or has a gastrointestinal disorder likely to interfere with absorption of the study medication.
Participant received whole blood transfusions in the 2 weeks prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 2 weeks prior to treatment).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort C (Niraparib)	Niraparib	-
Cohort C (Carboplatin + Paclitaxel)	Carboplatin	-
Cohort C (Carboplatin + Paclitaxel)	Paclitaxel	-

Primary Outcome Measures

Name	Time	Method
Pre-Interval Debulking Surgery (IDS) Unconfirmed Overall Response Rate (ORR)	Up to approximately 102 weeks	Pre-IDS unconfirmed ORR is defined as the percentage of participants with unconfirmed complete or partial response on study treatment pre-IDS as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the Investigator. Complete Response (CR) is defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Cancer Antigen (CA)-125 Progression by GCIG CA-125 Response Criteria	Up to approximately 206 weeks	Serum samples will be collected to determine CA-125 progression by Gynecological Cancer Intergroup (GCIG) CA-125 response criteria
Overall Survival (OS)	Up to approximately 206 weeks	OS, defined as the time from the date of treatment randomization to the date of death by any cause
Time to First Subsequent Treatment (TFST)	Up to approximately 206 weeks	TFST, defined as the time from the date of treatment randomization to the date of first subsequent anticancer therapy or death
Number of Participants With Change in Frequency and Severity of Items as Measured by Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Up to approximately 206 weeks	The PRO-CTCAE is a patient-reported outcome measure that was developed to evaluate symptomatic toxicities in patients in cancer clinical trials; it characterizes the frequency, severity, interference, and presence or absence of symptomatic toxicities. Responses ranges from 0 ("never," "none," "not at all," or "absent") to 4 ("almost constantly," "very severe," or "very much"), with a higher score indicating a higher frequency, severity, or interference of adverse events.
Progression Free Survival (PFS)	Up to approximately 206 weeks	PFS, defined as the time from the date of treatment randomization to the date of first documentation of PD per RECIST v1.1 or death by any cause, whichever occurs first, as determined by the Investigator
Change From Baseline in Overall Side Effect Bother as Measured by Functional Assessment of Cancer Therapy - Item FACT-GP5	Up to approximately 206 weeks	The FACT-GP5 item is a single item from the FACT-G that assesses how bothersome the side effects of treatment are for cancer patients. The item has a 5-category response scale ranging from "0=Not at all" or "no bother" to "4=Very much" or "a lot of bother". Higher scores indicate the side effects are more bothersome.
Change From Baseline in European Organisation for Research and Treatment of Cancer Item Library 136 (EORTC IL136)	Up to approximately 206 weeks	EORTC IL136 consists of specific items from the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 is a 30-item survey designed to assess various aspects of health-related quality of life (HRQoL) in cancer patients. This questionnaire includes both multi-item scales and single-item measures, covering 5 functional scales, 3 symptom scales, 6 single items, and a global health status/HRQoL scale. The functional and symptom scales/items are rated on a 4-point scale with options "Not at all," "A little," "Quite a bit," and "Very much." The 2 items measuring global health status/quality of life use a 7-point scale ranging from 1 ("Very Poor") to 7 ("Excellent"). Each item has a specific scoring system, and the scores are transformed to a 0-100 scale
Change From Baseline in European Organisation for Research and Treatment of Cancer Item Library 137 (EORTC IL137)	Up to approximately 206 weeks	The OC module (QLQ-OV28) supplements the QLQ-C30 and was designed for participants with local or advanced disease who receive treatment by surgery with or without chemotherapy. It consists of 28 items and includes 3 functional scales (body image, sexuality, and attitude to disease/treatment burden) and 5 symptom scales/items (abdominal/gastrointestinal symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side effects, and hair loss). The scoring approach for the OC module is identical in principle to that used for the scales/items of the EORTC QLQ-C30. A subset of the questions (9 questions) will be utilized for this cohort and will be referred to as the EORTC IL137.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and AE of Special Interest (AESIs) by Severity	Up to approximately 206 weeks	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, is life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function. SAEs are subsets of AEs. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state. AESIs for this study are myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or second primary cancer (new malignancies other than MDS or AML). AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
Number of Participants With Dose Modification Due to Adverse Events (AEs)	Up to approximately 206 weeks	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be coded using the MedDRA coding system.