Clinical trial NCT06964165: 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)
Official title: Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter Study Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in Participants With Homologous Recombination-Deficient Stage III/IV Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Keywords: Ovarian Cancer
Homologous Recombination Deficiency (HRD)
Interval debulking surgery (IDS)
Niraparib
Paclitaxel
Carboplatin
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-09
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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).

Primary outcomes:
measure: Pre-Interval Debulking Surgery (IDS) unconfirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 26 months
Secondary outcomes:
measure: Number of participants with cancer antigen (CA)-125 progression
timeFrame: Up to approximately 35 months
measure: Progression free survival (PFS)
timeFrame: Up to approximately 35 months
measure: 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)
timeFrame: Up to approximately 35 months
measure: Change from baseline in overall side effect bother as measured by Functional Assessment of Cancer Therapy - Item FACT-GP5
timeFrame: Up to approximately 35 months
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer Item Library 136 (EORTC IL136)
timeFrame: Up to approximately 35 months
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Item Library 137 (EORTC IL137)
timeFrame: Up to approximately 35 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 35 months
measure: Time to first subsequent therapy (TFST)
timeFrame: Up to approximately 35 months
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 35 months
measure: Number of Participants with TEAEs and SAEs by severity
timeFrame: Up to approximately 35 months
measure: Number of Participants with treatment discontinuations or dose delays or reductions due to Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 35 months
measure: Number of participants with changes in Eastern Cooperative Oncology Group (ECOG) performance status, clinical laboratory results (hematology and chemistry) and vital sign measurements
timeFrame: Up to approximately 35 months
measure: Number of participants with clinically significant observations in symptom-directed physical examination
timeFrame: Up to approximately 35 months
measure: Number of participants with use of concomitant medications
timeFrame: Up to approximately 35 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Scarborough
country: United States
facility: GSK Investigational Site
state: Maine
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: A Coruña
country: Spain
facility: GSK Investigational Site
state: ES
city: Madrid
country: Spain
facility: GSK Investigational Site
state: ES
city: Madrid
country: Spain
facility: GSK Investigational Site
state: ES
city: Madrid
country: Spain
facility: GSK Investigational Site
state: ES
city: Madrid
country: Spain
facility: GSK Investigational Site
state: ES
city: Málaga
country: Spain
facility: GSK Investigational Site
state: ES
city: Pamplona
country: Spain
facility: GSK Investigational Site
state: ES
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: