Ovarian Neoplasms
Conditions
Keywords
Ovarian Cancer, Niraparib, GSK3985771, Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP)Inhibitor, Homologous recombination deficiency (HRD), HRD positive, PRIMA, PRIMA Clinical Trial, PRIMA Study
Brief summary
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.
Interventions
DRUGNiraparib
Niraparib will be administered.
DRUGPlacebo
Placebo will be administered.
Sponsors
Tesaro, Inc.
Gynecologic Oncology Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Participant received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment. 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 34 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 34 months | 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. |
| Time to First Subsequent Therapy (TFST) | Up to 34 months | 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. |
| Progression-Free Survival-2 (PFS2) | Up to 34 months | 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. |
| Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) | Baseline (Day 1, Pre-dose) and Up to Week 24 | 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). |
| Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score | Baseline (Day 1, Pre-dose) and Up to Week 24 | 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). |
| Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Baseline (Day 1, Pre-dose) and Up to Week 24 | 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). |
| Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30 | Baseline (Day 1, Pre-dose) and Up to Week 24 | 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). |
| Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Baseline (Day 1, Pre-dose) and Up to Week 24 | 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). |
| 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) | Baseline (Day 1, Pre-dose) and Up to 34 months | 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). |
| Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Baseline (Day 1, Pre-dose) and Up to 34 months | 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). |
Countries
Belgium, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Norway, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
In this double-blind, randomized, placebo-controlled study, participants with stage III or IV ovarian cancer were randomized to receive either niraparib or placebo in 2:1 ratio. The results presented are based on the primary analysis up to month 34. Data collection is still on-going and additional results will be provided after study completion (7 years).
Pre-assignment details
A total of 989 participants were screened, of which 256 participants did not meet eligibility criteria. A total of 733 participants were enrolled and randomized in the study, of which 728 participants received study treatment (4 participants were screen failures after randomization and 1 participant withdrew consent before first dose).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight \>=77 kilogram \[kg\] and Baseline platelet count \>=150,000 per microliter \[μL\]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight \<77 kg or Baseline platelet count \<150,000 per μL). | 246 |
| Niraparib Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight \>=77 kg and Baseline platelet count \>=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight \<77 kg or Baseline platelet count \<150,000 per μL). | 487 |
| Total | 733 |
Baseline characteristics
| Characteristic | Placebo | Niraparib | Total |
|---|---|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 10.39 | 61.1 Years STANDARD_DEVIATION 10.79 | 61.2 Years STANDARD_DEVIATION 10.65 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 14 Participants | 25 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 10 Participants | 12 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 14 Participants | 25 Participants | 39 Participants |
| Race/Ethnicity, Customized White | 219 Participants | 436 Participants | 655 Participants |
| Sex: Female, Male Female | 246 Participants | 487 Participants | 733 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 31 / 244 | 48 / 484 |
| other Total, other adverse events | 223 / 244 | 478 / 484 |
| serious Total, serious adverse events | 32 / 244 | 156 / 484 |
Outcome results
Primary
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.
Time frame: Up to 34 months
Population: Intent-to-Treat (ITT) population comprised of all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Progression Free Survival | 8.2 Months |
| Niraparib | Progression Free Survival | 13.8 Months |
p-value: <0.000195% CI: [0.502, 0.755]Log Rank
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to Week 24
Population: ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Role Functioning, n=244,479 | 2.341 Scores on a scale | Standard Error 1.2427 |
| Placebo | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Cognitive Functioning, n=243,478 | -0.020 Scores on a scale | Standard Error 1.2105 |
| Placebo | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Emotional Functioning, n=243,478 | -0.011 Scores on a scale | Standard Error 1.1218 |
| Placebo | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Social Functioning, n=243,478 | 5.557 Scores on a scale | Standard Error 1.2449 |
| Placebo | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Physical Functioning, n=244,479 | 2.119 Scores on a scale | Standard Error 0.8131 |
| Niraparib | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Social Functioning, n=243,478 | 4.445 Scores on a scale | Standard Error 0.8633 |
| Niraparib | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Physical Functioning, n=244,479 | 2.013 Scores on a scale | Standard Error 0.5735 |
| Niraparib | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Role Functioning, n=244,479 | 1.590 Scores on a scale | Standard Error 0.881 |
| Niraparib | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Emotional Functioning, n=243,478 | -0.870 Scores on a scale | Standard Error 0.7685 |
| Niraparib | Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Cognitive Functioning, n=243,478 | -0.842 Scores on a scale | Standard Error 0.7952 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to 34 months
Population: ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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) | Body Image, n=244,475 | 10.069 Scores on a scale | Standard Error 1.482 |
| Placebo | 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) | Sexuality, n=240,471 | 3.257 Scores on a scale | Standard Error 1.1886 |
| Placebo | 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) | Attitude to disease/Treatment, n=244,475 | 12.216 Scores on a scale | Standard Error 1.3257 |
| Niraparib | 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) | Body Image, n=244,475 | 8.488 Scores on a scale | Standard Error 1.0138 |
| Niraparib | 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) | Sexuality, n=240,471 | 3.625 Scores on a scale | Standard Error 0.8004 |
| Niraparib | 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) | Attitude to disease/Treatment, n=244,475 | 13.660 Scores on a scale | Standard Error 0.9309 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to Week 24
Population: ITT Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30 | 1.177 Scores on a scale | Standard Error 1.0005 |
| Niraparib | Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30 | 1.009 Scores on a scale | Standard Error 0.6898 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to Week 24
Population: ITT Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) | -0.3 Scores on a scale | Standard Error 0.22 |
| Niraparib | Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) | -0.4 Scores on a scale | Standard Error 0.15 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to Week 24
Population: ITT Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score | 0.005 Scores on a scale | Standard Error 0.0066 |
| Niraparib | Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score | 0.016 Scores on a scale | Standard Error 0.0046 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to 34 months
Population: ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Peripheral Neuropathy, n=244,480 | -9.629 Scores on a scale | Standard Error 1.3219 |
| Placebo | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Other Chemotherapy Side Effects, n=244,480 | -3.023 Scores on a scale | Standard Error 0.8358 |
| Placebo | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Hormonal/Menopausal Symptoms, n=244,480 | -2.521 Scores on a scale | Standard Error 1.3074 |
| Placebo | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Hair Loss, n=242,477 | -20.743 Scores on a scale | Standard Error 1.369 |
| Placebo | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Abdominal/GI, n=244,481 | 0.832 Scores on a scale | Standard Error 0.811 |
| Niraparib | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Hair Loss, n=242,477 | -23.363 Scores on a scale | Standard Error 0.9821 |
| Niraparib | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Abdominal/GI, n=244,481 | 2.185 Scores on a scale | Standard Error 0.5703 |
| Niraparib | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Peripheral Neuropathy, n=244,480 | -8.217 Scores on a scale | Standard Error 0.9295 |
| Niraparib | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Hormonal/Menopausal Symptoms, n=244,480 | 1.501 Scores on a scale | Standard Error 0.8803 |
| Niraparib | Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 | Other Chemotherapy Side Effects, n=244,480 | -2.219 Scores on a scale | Standard Error 0.5581 |
Secondary
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).
Time frame: Baseline (Day 1, Pre-dose) and Up to Week 24
Population: ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Nausea/Vomiting, n=244,479 | 1.673 Scores on a scale | Standard Error 0.7595 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Appetite Loss, n=8,30 | -0.827 Scores on a scale | Standard Error 4.3987 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Dyspnea, n=244,479 | 0.644 Scores on a scale | Standard Error 1.3592 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Constipation, n=244,478 | -1.147 Scores on a scale | Standard Error 1.5793 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Pain, n=244,480 | -0.195 Scores on a scale | Standard Error 1.2274 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Diarrhea, n=8,30 | 9.335 Scores on a scale | Standard Error 3.8667 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Insomnia, n=244,479 | 2.195 Scores on a scale | Standard Error 1.9882 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Financial Difficulties, n=243,475 | -5.058 Scores on a scale | Standard Error 1.2978 |
| Placebo | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Fatigue, n=243,479 | -0.082 Scores on a scale | Standard Error 1.2394 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Financial Difficulties, n=243,475 | -3.356 Scores on a scale | Standard Error 0.9276 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Fatigue, n=243,479 | 0.085 Scores on a scale | Standard Error 0.8363 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Nausea/Vomiting, n=244,479 | 3.115 Scores on a scale | Standard Error 0.4828 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Pain, n=244,480 | 0.765 Scores on a scale | Standard Error 1.0166 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Dyspnea, n=244,479 | 1.347 Scores on a scale | Standard Error 0.8518 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Insomnia, n=244,479 | 3.478 Scores on a scale | Standard Error 1.2791 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Appetite Loss, n=8,30 | -0.395 Scores on a scale | Standard Error 2.3195 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Constipation, n=244,478 | 6.356 Scores on a scale | Standard Error 1.0446 |
| Niraparib | Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 | Diarrhea, n=8,30 | -3.340 Scores on a scale | Standard Error 2.0136 |
Secondary
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.
Time frame: Up to 34 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival | NA Months |
| Niraparib | Overall Survival | 30.3 Months |
p-value: 0.123895% CI: [0.442, 1.106]Log Rank
Secondary
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.
Time frame: Up to 34 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Progression-Free Survival-2 (PFS2) | NA Months |
| Niraparib | Progression-Free Survival-2 (PFS2) | 27.2 Months |
p-value: 0.224295% CI: [0.577, 1.139]Log Rank
Secondary
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.
Time frame: Up to 34 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Subsequent Therapy (TFST) | 12.0 Months |
| Niraparib | Time to First Subsequent Therapy (TFST) | 18.6 Months |
p-value: 0.000195% CI: [0.521, 0.802]Log Rank
Other Pre-specified
Area Under the Curve (AUC) From 0 to the Last Quantifiable Concentration (AUC[0-last])
Blood samples were planned to be collected for assessment of AUC(0-last).
Time frame: Up to 34 months
Population: ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Other Pre-specified
Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE
An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time frame: Up to 34 months
Population: Safety Population comprised of all participants who received at least 1 dose of study drug. 5 participants (2 participants from Placebo group and 3 participants from Niraparib group) out of 733 participants did not receive any study treatment and thus, were excluded from the Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE | Any non-SAE | 223 Participants |
| Placebo | Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE | Any SAE | 32 Participants |
| Niraparib | Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE | Any non-SAE | 478 Participants |
| Niraparib | Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE | Any SAE | 156 Participants |
Other Pre-specified
Number of Participants With Positive HRD Test
Number of participants with positive HRD test was planned to be assessed.
Time frame: Up to 34 months
Population: ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Other Pre-specified
Peak Plasma Concentration (Cmax)
Blood samples were planned to be collected for assessment of Cmax.
Time frame: Up to 34 months
Population: ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.