A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer

Phase 3

Completed

Conditions: Ovarian Neoplasms
Platinum Sensitive Ovarian Cancer

Interventions: Drug: placebo

Registration Number: NCT01847274

Lead Sponsor: Tesaro, Inc.

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 596

Inclusion Criteria

18 years of age or older, female, any race
Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
High grade (or grade 3) serous histology or known to have gBRCAmut
Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
ECOG 0-1
Adequate bone marrow, kidney and liver function

Exclusion Criteria

Known hypersensitivity to the components of niraparib
Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
Symptomatic uncontrolled brain metastasis
Is pregnant or breast feeding
Immunocompromised patients
Known active hepatic disease
Prior treatment with a known PARP inhibitor

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Administered once daily continuously over a 28 day cycle.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)	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	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.
Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)	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	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.
Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation	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	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.

Secondary Outcome Measures

Name	Time	Method
Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)	From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days	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 to First Subsequent Therapy in Cohort With No Germline BRCA Mutation	From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days	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
Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)	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	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 to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)	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	TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)	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 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
Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation	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 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
Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation	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	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.
Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)	From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days	Overall survival was defined as the date of randomization to the date of death by any cause.
Overall Survival in Cohort With No Germline BRCA Mutation	From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days	Overall survival was defined as the date of randomization to the date of death by any cause.
Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation	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	TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2	Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6	At Cycle 6 (Each cycle was of 28 days)	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").
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6	At Cycle 6 (Each cycle was of 28 days)	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").
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4	Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)	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.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6	Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)	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.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression	Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days	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.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2	Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression	Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4	At Cycle 4 (Each cycle was of 28 days)	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").
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4	Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4	Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6	Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)	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.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6	Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)	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.
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression	Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days	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.
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6	Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline	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.
Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study	Up to 7 years, 7 months and 4 days	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2	At Cycle 2 (Each cycle was of 28 days)	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").
Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2	Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2	Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4	Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)	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.
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression	Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression	Up to 7 years, 7 months and 4 days	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").
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression	Up to 7 years, 7 months and 4 days	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").
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline	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.
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2	At Cycle 2 (Each cycle was of 28 days)	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").
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4	At Cycle 4 (Each cycle was of 28 days)	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").
Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study	Up to 7 years, 7 months and 4 days	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.
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)	Up to 7 years, 7 months and 6 days	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.
Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding)	Up to 8 months, 26 days	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
Number of Participants With Non-serious AEs and SAEs in FE Sub-study	Up to 2 years, 3 months and 11 days	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.
Number of Participants With Non-serious AEs and SAEs in QTc Sub-study	Up to 5 years 10 months and 22 days	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.
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study)	Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose	Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib.
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)	Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose	Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib.
Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study)	Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose	Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib.
Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study)	Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose	Blood samples were collected at indicated time points to analyze the tmax of niraparib.
Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study)	Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose	Blood samples were collected at indicated time points to analyze the t1/2 of niraparib.
Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds	At Baseline (Cycle 1 Day 1, each cycle was of 28 days)	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.

Trial Locations

Locations (1): GSK Investigational Site
🇬🇧
Taunton, United Kingdom

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