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 2TerminatedNCT06964165

Tesaro, Inc.36 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ovarian Neoplasms

Interventions

NiraparibDRUG

Niraparib will be administered

CarboplatinDRUG

Carboplatin will be administered

PaclitaxelDRUG

Paclitaxel will be administered

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (21)

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Miami, Florida, United States

Outcomes

Primary Outcomes

Pre-Interval Debulking Surgery (IDS) Unconfirmed Overall Response Rate (ORR)

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

Time frame: Up to approximately 102 weeks

Secondary Outcomes

Number of Participants With Cancer Antigen (CA)-125 Progression by Gynecological Cancer InterGroup (GCIG) CA-125 Response Criteria

Serum samples were collected to assess CA-125 progression based on the GCIG CA-125 response criteria, which is defined as follows: Criteria 1 - For participants with elevated CA-125 levels pre-treatment that reduced to the normal range during the study, progression is defined as CA-125 ≥2× Upper limit of normal (ULN) on 2 occasions at least 1 week apart.; Criteria 2 - For participants with elevated CA-125 levels pre-treatment that did not reduce to the normal range during the study, progression is defined as CA-125 ≥2× the nadir value on 2 occasions at least 1 week apart.; Criteria 3 - For participants with CA-125 levels in the normal range pre-treatment, progression is defined as CA-125 ≥2× ULN on 2 occasions at least 1 week apart.

Time frame: At week 24

Progression Free Survival (PFS)

PFS is defined as the time from the date of treatment randomization to the date of first documentation of disease progression (PD) per RECIST v1.1 or death by any cause, whichever occurs first, as determined by the Investigator. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.

Data from ClinicalTrials.gov

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GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Scarborough, Maine, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Rochester, New York, United States

GSK Investigational Site

Sioux Falls, South Dakota, United States

...and 11 more locations

Time frame: Up to approximately 154 weeks

Overall Survival (OS)

OS is defined as the time from the date of treatment randomization to the date of death by any cause.

Time frame: Up to approximately 154 weeks

Time to First Subsequent Treatment (TFST)

TFST is defined as the time from the date of treatment randomization to the date of first subsequent anticancer therapy or death.

Time frame: Up to approximately 154 weeks

Number of Participants With Frequency and Severity of Items as Measured by Patient Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants of cancer clinical studies. It characterizes the frequency and severity of adverse events using a standardized scoring system. Responses include 0 ("never" OR "none" OR "Not at all"); 1 ("Rarely" OR "Mild" OR "A little bit"); 2 ("Occasionally" OR "Moderate" OR "Somewhat"); 3 ("Frequently" OR "Severe" OR "Quite a bit") and 4 ("almost constantly" OR "very severe" OR "Very much"), with a higher score indicating a higher frequency and severity of adverse events.

Time frame: Baseline (Predose), Day 8 and 15 of Cycle 1; Day 1, 8 and 15 of Cycle 2 and Cycle 3; Pre-IDS Evaluation, and End of Treatment (Up to approximately 154 weeks).

Number of Participants With Overall Side Effect Bother as Measured by Functional Assessment of Cancer Therapy - Item FACT-GP5

The FACT-GP5 item is a single item from the FACT-G that assesses how bothersome the side effects of treatment are for participants with cancer. It evaluates the extent to which side effects of treatment are bothersome for cancer participants. This outcome is measured using a 5-category response scale, where responses include 0="Not at all," 1="A little bit," 2="Somewhat," 3="Quite a bit," and 4="Very much." A higher score on this measure indicates that the participant experiences a greater level of bother from the side effects of treatment.

Time frame: Baseline (Predose), Day 8 and 15 of Cycle 1; Day 1, 8, and 15 of Cycle 2 and Cycle 3; Pre-IDS Evaluation, and End of Treatment (Up to approximately 154 weeks)

Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Item Library 136 (EORTC IL136) Questionnaire

EORTC IL136 includes items from the EORTC QLQ-C30, a 30-item survey assessing health-related quality of life (HRQoL) in cancer patients, featuring 5 functional scales, 3 symptom scales, 6 single items, and a global health status/HRQoL scale. Functional and symptom scales/items are rated on 4-point scale with options "Not at all," "A little," "Quite a bit," and "Very much". 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 scores were transformed to a 0-100 scale, where higher scores on functional scales and global health status/HRQoL scale indicate better functioning or quality of life, while higher scores on symptom scales/items indicate greater symptom burden. Baseline is defined as the latest assessment with a non-missing value prior to Cycle 1 Day 1 (C1D1), including those from unscheduled visits.

Time frame: Baseline (Predose), Day 1 of Cycle 2 and Cycle 3; Pre-IDS Evaluation, and End of Treatment (Up to approximately 154 weeks).

Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Item Library 137 (EORTC IL137) Questionnaire

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 including 3 functional scales (body image, sexuality, 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). A subset of 9 questions will be utilized for this cohort, referred to as the EORTC IL137. The scoring approach is identical to the EORTC QLQ-C30. Scores are transformed to a 0-100 scale, where higher functional scale scores indicate better functioning, and higher symptom scale scores indicate greater symptom burden. Baseline is defined as the latest assessment with a non-missing value prior to C1D1, including unscheduled visits.

Time frame: Baseline (Predose), Day 1 of Cycle 2 and Cycle 3; Pre-IDS Evaluation, and End of Treatment (Up to approximately 154 weeks).

Number of Participants With Treatment Emergent (TE) Non-serious Adverse Events (Non-SAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Treatment Emergent (TE) Special Interest (AESIs) by Severity

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. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.

Time frame: Up to approximately 154 weeks

Number of Participants With Dose Modification Due to TEAEs

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. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state. Number of participants with dose modifications : permanent discontinuation, dose reduction and treatment interruption/delay due to AEs is summarized.

Time frame: Up to approximately 154 weeks