A Study of Niraparib (GSK3985771) Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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This study aims to assess efficacy of Niraparib (GSK3985771) as maintenance treatment in participants with Stage III or IV ovarian cancer. Participants must have completed front-line platinum based regimen with complete response (CR) or partial response (PR). Data collection for Secondary Outcome measures is ongoing and the approximate duration of the study will be 7 years.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Drug: Niraparib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants must have histologically diagnosed high-grade serous or endometrioid, or high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to Federation Internationale de Gynécologie et d'Obstétrique (FIGO) criteria. Participants with inoperable Stage III and IV disease; All Stage IV participants with operable disease; Participants with stage III or IV disease treated with neoadjuvant chemotherapy and interval debulking surgery; and Participants with stage III disease who have visible residual disease after primary debulking surgery. Participants who have received intraperitoneal chemotherapy; All participants must have had more than or equal to (>=)6 and less than or equal to (<=)9 cycles of platinum-based therapy; Participants must have had >=2 post-operative cycles of platinum-based therapy following interval debulking surgery; Participants must have physician assessed Complete response (CR) or Partial response (PR) after >=3 cycles of therapy; and Participants must have either Cancer antigen 125 (CA-125) in the normal range or CA-125 decrease by more than 90 percent(%) during their front-line therapy that is stable for at least 7 days (no increase more than (>)15% from nadir). Participants must be randomized within 12 weeks of the first day of the last cycle of chemotherapy. All participants must agree to undergo central tumor HRD testing. Participants of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin [hCG]) within 7 days prior to receiving the first dose of study treatment. Exclusion criteria: Participant has mucinous or clear cell subtypes of epithelial ovarian cancer, carcinosarcoma or undifferentiated ovarian cancer. Participants with Stage III disease who have had complete cytoreduction (no visible residual disease) after primary debulking surgery. Participant has undergone more than two debulking surgeries for the study disease. Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for up to 180 days after the last dose of study treatment. Participant has a known hypersensitivity to the components of niraparib or its excipients. Participant has received prior treatment with a known PARP inhibitor or has participated in a study where any treatment arm included administration of a known PARP inhibitor. Participant is to receive bevacizumab as maintenance treatment. Participant has had investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study. Participant has had any known >=Grade 3 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted >4 weeks. Participant has a condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the participation for the full duration of the study treatment, including: Participant received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment. Participant received colony-stimulating factors (e.g., granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment. Participant has been diagnosed and/or treated for invasive cancer less than 5 years prior to study enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving Niraparib<br> | Drug: Niraparib<br>* Niraparib will be administered.<br>|
| Placebo Comparator: Participants receiving Placebo<br> | Drug: Placebo<br>* Placebo will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival was defined as the time from the date of treatment randomization to the date of first documentation of disease progression or death due to any cause in the absence of documented progression, whichever occurs first. It was assessed by the blinded independent central review (BICR). Median and 95% confidence interval (CI) are presented. | Up to 34 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from the date of randomization to the date of death by any cause. Median and 95% CI are presented for overall survival interim analysis. | Up to 34 months | 
| Time to First Subsequent Therapy (TFST) | Time to first subsequent therapy was defined as the time from the date of randomization to the date of the first subsequent anti-cancer therapy or death, whichever occurs first. Median and 95% CI are presented. | Up to 34 months | 
| Progression-Free Survival-2 (PFS2) | PFS2 was defined as the time from the date of randomization to the date of progression on the next anti-cancer therapy following study treatment or death by any cause, whichever occurs first. Median and 95% CI are presented. | Up to 34 months | 
| Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) | FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants responded to their symptom experience over the past 7 days using a 5-point Likert scale scored from not at all (0) to very much (4). FOSI score was calculated as (sum of item scores)*8 divided by (number of items answered). The FOSI score ranged from 0 (severely symptomatic) to 32 (asymptomatic). A higher score indicated a better quality of life (QoL). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to Week 24 | 
| Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score | The EQ-5D-5L is a well-validated general preference-based, health-related QoL instrument. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to Week 24 | 
| Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Five functional scales had total 15 items (physical-5, role-2, cognitive-4, emotional-2, and social-2). Each functional scales score was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher (better) level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to Week 24 | 
| Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30 | EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. A global health status/QoL scale had total 2 items. Each global health status/QoL scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 6*100). The global health status/QoL scales range in score from 0 to 100. Higher score represents a higher (better) level of health status/QoL. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to Week 24 | 
| Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale, and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Symptom scale had total 7 items (fatigue-3, pain-2, nausea/vomiting-2). Each symptoms scales and 6 single additional symptoms items score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales and 6 single additional symptoms scales range in score from 0 to 100. Higher score represents a higher (worse) level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to Week 24 | 
| Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer Module (EORTC-QLQ-OV28) | EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/gastrointestinal [GI] symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Functional scales score (body Image and attitude to disease/treatment) was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). Functional scales score (sexuality) was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher (better) level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to 34 months | 
| Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/GI symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Symptoms scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales range in score from 0 to 100. Higher score represents a higher (worse) level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). | Baseline (Day 1, Pre-dose) and Up to 34 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Niraparib, GSK3985771, Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP)Inhibitor, Homologous recombination deficiency (HRD), HRD positive, PRIMA, PRIMA Clinical Trial, PRIMA Study