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

• ClinicalTrials.gov Identifier: NCT01847274
• Recruitment Status: Completed
• First Posted: May 6, 2013
• Results First Posted: May 1, 2019
• Last Update Posted: June 2, 2023
• Sponsor: Tesaro, Inc.
• Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT); Myriad Genetics, Inc.; US Oncology Research; Sarah Cannon; Cooperative Ovarian Cancer Group (COGI); Facing Our Risk of Cancer Empowered
• Information provided by (Responsible Party): Tesaro, Inc.

Tracking Information

• First Submitted Date: April 11, 2013
• First Posted Date: May 6, 2013
• Results First Submitted Date: October 18, 2018
• Results First Posted Date: May 1, 2019
• Last Update Posted Date: June 2, 2023
• Actual Study Start Date: June 21, 2013
• Actual Primary Completion Date: April 22, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2022)

• Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) [ 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 ]
  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+) [ 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 ]
  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 [ 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 ]
  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.

Original Primary Outcome Measures (submitted: May 3, 2013)

Progression free survival of ovarian cancer patients [ Time Frame: 35 months ]

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).

Current Secondary Outcome Measures (submitted: March 31, 2023)

• Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) [ 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 ]
  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 [ 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 ]
  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
• Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) [ 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 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 [ 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 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 Germline BRCA Mutation (gBRCA) [ 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 ]
  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.
• Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation [ 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 ]
  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) [ Time Frame: 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 [ Time Frame: 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 Germline BRCA Mutation (gBRCA) [ 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 ]
  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 to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation [ 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 ]
  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 [ Time Frame: 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 Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
  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 [ Time Frame: 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 Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4 [ Time Frame: 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 no Germline BRCA at Cycle 6 [ Time Frame: 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 [ Time Frame: 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 European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 [ Time Frame: 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 Germline BRCA at Cycle 4 [ Time Frame: 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 [ Time Frame: 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 EQ-5D-5L in Cohort With Germline BRCA at Post-progression [ Time Frame: 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.
• Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2 [ Time Frame: 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 [ Time Frame: 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 Cycle 6 [ Time Frame: 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 EQ-5D-5L in Cohort With no Germline BRCA at Post-progression [ Time Frame: 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 Baseline [ Time Frame: 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 Germline BRCA at Cycle 2 [ Time Frame: 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 Germline BRCA at Cycle 4 [ Time Frame: 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 Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 [ Time Frame: 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 Germline BRCA at Post-progression [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 [ Time Frame: 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 Post-progression [ Time Frame: 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 Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study [ Time Frame: 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 Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ 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 ]
  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) [ 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 ]
  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) [ 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 ]
  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) [ 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 ]
  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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: May 3, 2013)

• Patient Reported Outcomes [ Time Frame: 35 months ]
  Functional Assessment of Cancer therapy - Ovarian Symptom Index (FOSI) EQ-5D-5L Neuropathy Questionnaire
• Progression Free Survival Two [ Time Frame: 35 months ]
  Time from treatment randomization to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death by any cause.
• Chemotherapy Free Interval [ Time Frame: 35 Months ]
  Chemotherapy free interval (CFI) is the time from last platinum dose until initiation of the next anticancer therapy
• Overall Survival of Ovarian Cancer Patients [ Time Frame: 35 Months ]
• Evaluate the safety and tolerability of niraparib in ovarian cancer patients [ Time Frame: 35 months ]
  Review of adverse events, physical exams, electrocardiograms (ECGs), and safety lab values
• BRACA diagnostic test [ Time Frame: 35 months ]
  Concordance of a candidate companion diagnostic test compared to centralized BRCA mutation test

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer
• Official Title: A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer.

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Ovarian Neoplasms
• Platinum Sensitive Ovarian Cancer

Intervention

• Drug: Active comparator: Niraparib
  Niraparib vs placebo 2:1 ratio
  Other Name: Niraparib
• Drug: placebo

Study Arms

• Active Comparator: Niraparib
  2:1 Ratio administered once daily continuously during a 28 day cycle.
  Intervention: Drug: Active comparator: Niraparib
• Placebo Comparator: Placebo
  Administered once daily continuously over a 28 day cycle.
  Intervention: Drug: placebo

Publications *

• Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.
• Mirza MR, Lindahl G, Mahner S, Redondo A, Fabbro M, Rimel BJ, Herrstedt J, Oza AM, Canzler U, Berek JS, Gonzalez-Martin A, Follana P, Lord R, Azodi M, Estenson K, Wang Z, Li Y, Gupta D, Matulonis U, Feng B. Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects. Cancer Res Commun. 2022 Nov 15;2(11):1436-1444. doi: 10.1158/2767-9764.CRC-22-0240. eCollection 2022 Nov.
• Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
• Mirza MR, Benigno B, Dorum A, Mahner S, Bessette P, Barcelo IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Herraez AC, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. doi: 10.1016/j.ygyno.2020.09.006. Epub 2020 Sep 25.
• Matulonis UA, Walder L, Nottrup TJ, Bessette P, Mahner S, Gil-Martin M, Kalbacher E, Ledermann JA, Wenham RM, Woie K, Lau S, Marme F, Casado Herraez A, Hardy-Bessard AC, Banerjee S, Lindahl G, Benigno B, Buscema J, Travers K, Guy H, Mirza MR. Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Dec 1;37(34):3183-3191. doi: 10.1200/JCO.19.00917. Epub 2019 Sep 16.
• Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. doi: 10.1200/JCO.18.02238. Epub 2019 Jun 7.
• Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vazquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. doi: 10.1016/S1470-2045(18)30333-4. Epub 2018 Jul 17.
• Berek JS, Matulonis UA, Peen U, Ghatage P, Mahner S, Redondo A, Lesoin A, Colombo N, Vergote I, Rosengarten O, Ledermann J, Pineda M, Ellard S, Sehouli J, Gonzalez-Martin A, Berton-Rigaud D, Madry R, Reinthaller A, Hazard S, Guo W, Mirza MR. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018 Aug 1;29(8):1784-1792. doi: 10.1093/annonc/mdy181. Erratum In: Ann Oncol. 2019 May 1;30(5):859.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 16, 2022): 596
• Original Estimated Enrollment (submitted: May 3, 2013): 360
• Actual Study Completion Date: December 26, 2021
• Actual Primary Completion Date: April 22, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Norway, Poland, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT01847274
• Other Study ID Numbers: 213356; PR-30-5011-C ( Other Identifier: Tesaro )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tesaro, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tesaro, Inc.
• Original Study Sponsor: Same as current

Collaborators

• European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Myriad Genetics, Inc.
• US Oncology Research
• Sarah Cannon
• Cooperative Ovarian Cancer Group (COGI)
• Facing Our Risk of Cancer Empowered

Investigators

• Study Director: GSK Clinical Studies; GlaxoSmithKline

• PRS Account: Tesaro, Inc.
• Verification Date: May 2023