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)
- Conditions
- Ovarian Neoplasms
- Interventions
- 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
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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.
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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.
- 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.
- All participants must agree to provide tumor tissue collected from IDS.
- 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.
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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.
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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.
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Participant must not have known contraindication or uncontrolled hypersensitivity to niraparib and its excipients.
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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.
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Participant must agree to complete Patient-reported outcome (PRO) and work productivity questionnaires throughout the study.
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Participant has low-grade or Grade 1 epithelial Ovarian Cancer (OC) or mucinous, germ cell, transitional cell, carcinosarcoma, or undifferentiated tumor.
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Participant has contraindications to surgery.
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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.
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Participant has any known history or current diagnosis of Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).
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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).
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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:
- Cluster of differentiation 4-positive T cell count ≥350/μL and viral load <400 copies/mL
- No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months prior to enrollment
- No history of HIV-associated malignancy for the past 5 years
- 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
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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).
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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).
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Participant is unable to swallow orally administered medication or has a gastrointestinal disorder likely to interfere with absorption of the study medication.
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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 Objective Response Rate (ORR) Up to approximately 26 months ORR is defined as the percentage of participants with unconfirmed complete response (CR) or partial response (PR) on study treatment pre-IDS as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the investigator.
- Secondary Outcome Measures
Name Time Method Number of participants with cancer antigen (CA)-125 progression Up to approximately 35 months Serum samples will be collected to determine CA-125 progression by Gynecological Cancer InterGroup (GCIG) CA-125 response criteria
Progression free survival (PFS) Up to approximately 35 months PFS is defined as the time from the date of treatment randomization to the date of first documentation of progression of disease (PD) per RECIST v1.1 or death by any cause, whichever occurs first, as determined by the investigator
Overall Survival (OS) Up to approximately 35 months Time from the date of randomization to the date of death by any cause
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 35 months The PRO-CTCAE is a patient-reported outcome measure that was developed to evaluate symptomatic toxicities in participants 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.
Change from baseline in overall side effect bother as measured by Functional Assessment of Cancer Therapy - Item FACT-GP5 Up to approximately 35 months The FACT-GP5 item is a single item from the FACT-G that assesses how bothersome the side effects of treatment are for cancer participants 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 35 months The EORTC IL136 outcome uses selected items from the EORTC QLQ-C30, a 30-item survey evaluating health-related quality of life (HRQoL) in cancer participants. It includes multi-item scales and single-item measures: 5 functional scales, 3 symptom scales, 6 single items, and a global health/HRQoL scale. Functional and symptom items are rated on a 4-point scale from "Not at all" to "Very much." Global health status/QoL items use a 7-point scale from 1 ("Very Poor") to 7 ("Excellent"). Scores are transformed to a 0-100 scale. Higher functional scores denote better function, while higher symptom scores indicate more severe symptoms.
Change from baseline in European Organisation for Research and Treatment of Cancer Item Library 137 (EORTC IL137) Up to approximately 35 months The OC module (QLQ-OV28) supplements the QLQ-C30 for participants with local or advanced disease undergoing surgery with or without chemotherapy. It consists of 28 items, including 3 functional scales and 5 symptom scales/items. The scoring follows the EORTC QLQ-C30 approach. For this study, the subset EORTC IL137 uses 9 items analyzed as single items. Scores are transformed to a 0-100 scale; where higher functional scores signify better function and higher symptom scores indicate more severe symptoms.
Time to first subsequent therapy (TFST) Up to approximately 35 months TFST is defined as the time from the date of randomization to the date of the first subsequent anticancer therapy or death, whichever occurs first
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Up to approximately 35 months Number of Participants with TEAEs and SAEs by severity Up to approximately 35 months Number of Participants with treatment discontinuations or dose delays or reductions due to Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) Up to approximately 35 months Number of participants with changes in Eastern Cooperative Oncology Group (ECOG) performance status, clinical laboratory results (hematology and chemistry) and vital sign measurements Up to approximately 35 months Number of participants with clinically significant observations in symptom-directed physical examination Up to approximately 35 months Number of participants with use of concomitant medications Up to approximately 35 months
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Pamplona, ES, Spain