This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values. The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
596
Niraparib vs placebo 2:1 ratio
GSK Investigational Site
Phoenix, Arizona, United States
GSK Investigational Site
Tucson, Arizona, United States
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Palo Alto, California, United States
Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days
Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)
The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.
Time frame: From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days
Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation
The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death
Time frame: From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days
Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)
Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment
Time frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days
Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation
Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment
Time frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days
Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)
Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.
Time frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days
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GSK Investigational Site
San Francisco, California, United States
GSK Investigational Site
New Haven, Connecticut, United States
GSK Investigational Site
Sarasota, Florida, United States
GSK Investigational Site
Tampa, Florida, United States
GSK Investigational Site
Atlanta, Georgia, United States
...and 102 more locations
Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation
Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.
Time frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days
Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)
Overall survival was defined as the date of randomization to the date of death by any cause.
Time frame: From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days
Overall Survival in Cohort With No Germline BRCA Mutation
Overall survival was defined as the date of randomization to the date of death by any cause.
Time frame: From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days
Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)
TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Time frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days
Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation
TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Time frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit"). Baseline was latest non-missing pre-dose assessment on or before randomization date.
Time frame: At Baseline
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 2 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 4 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 6 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: Up to 7 years, 7 months and 4 days
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit"). Baseline was latest non-missing pre-dose assessment on or before randomization date.
Time frame: At Baseline
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 2 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 4 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: At Cycle 6 (Each cycle was of 28 days)
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").
Time frame: Up to 7 years, 7 months and 4 days
Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study
This will never be analyzed since the data for the candidate companion BRAC analysis diagnostic test was not collected which was to be compared with centralized BRCA mutation test used in this study.
Time frame: Up to 7 years, 7 months and 4 days
Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study
This will never be analyzed since the data for the candidate companion HRD diagnostic test was not collected which was to be compared with HRD test used in this study.
Time frame: Up to 7 years, 7 months and 4 days
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. Data presented for this outcome measure is based on the data cut-off date of 31-March-2021, which aligns with the time of the study unblinding.
Time frame: Up to 7 years, 7 months and 6 days
Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding)
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. The data is presented for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021
Time frame: Up to 8 months, 26 days
Number of Participants With Non-serious AEs and SAEs in FE Sub-study
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.
Time frame: Up to 2 years, 3 months and 11 days
Number of Participants With Non-serious AEs and SAEs in QTc Sub-study
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.
Time frame: Up to 5 years 10 months and 22 days
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib.
Time frame: Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the tmax of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the t1/2 of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds
12-lead electrocardiogram was obtained at indicated time points using an automated electrocardiogram machine that measured QTcF interval. The number of participants with maximum post-Baseline ECG value exceeding the following limits have been reported: QTcF interval \>450 and \<= 480 milliseconds (msec) and \>500 msec.
Time frame: At Baseline (Cycle 1 Day 1, each cycle was of 28 days)