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

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ClinicalTrials.gov Identifier: NCT02655016
Recruitment Status : Active, not recruiting
First Posted : January 13, 2016
Results First Posted : June 11, 2020
Last Update Posted : March 19, 2021
Sponsor:
Collaborators:
Gynecologic Oncology Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE December 8, 2015
First Posted Date  ICMJE January 13, 2016
Results First Submitted Date  ICMJE May 4, 2020
Results First Posted Date  ICMJE June 11, 2020
Last Update Posted Date March 19, 2021
Actual Study Start Date  ICMJE July 7, 2016
Actual Primary Completion Date May 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2020)
Progression Free Survival [ Time Frame: Up to 34 months ]
Progression free survival was defined as the time from the date of treatment randomization to the date of first documentation of disease progression or death due to any cause in the absence of documented progression, whichever occurs first. It was assessed by the blinded independent central review (BICR). Median and 95% confidence interval (CI) are presented.
Original Primary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
Progression Free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first - Approximately 10 months ]
The time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2020)
  • Overall Survival [ Time Frame: Up to 34 months ]
    Overall survival was defined as the time from the date of randomization to the date of death by any cause. Median and 95% CI are presented for overall survival interim analysis.
  • Time to First Subsequent Therapy (TFST) [ Time Frame: Up to 34 months ]
    Time to first subsequent therapy was defined as the time from the date of randomization to the date of the first subsequent anti-cancer therapy or death, whichever occurs first. Median and 95% CI are presented.
  • Progression-Free Survival-2 (PFS2) [ Time Frame: Up to 34 months ]
    PFS2 was defined as the time from the date of randomization to the date of progression on the next anti-cancer therapy following study treatment or death by any cause, whichever occurs first. Median and 95% CI are presented.
  • Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) [ Time Frame: Baseline (Day 1, Pre-dose) and Up to Week 24 ]
    FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants responded to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4). FOSI score was calculated as (sum of item scores)*8 divided by (number of items answered). The FOSI score ranged from 0 (severely symptomatic) to 32 (asymptomatic). A higher score indicated a better quality of life (QoL). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score [ Time Frame: Baseline (Day 1, Pre-dose) and Up to Week 24 ]
    The EQ-5D-5L is a well-validated general preference-based, health-related QoL instrument. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) [ Time Frame: Baseline (Day 1, Pre-dose) and Up to Week 24 ]
    EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Five functional scales had total 15 items (physical-5, role-2, cognitive-4, emotional-2, and social-2). Each functional scales score was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher ("better") level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30 [ Time Frame: Baseline (Day 1, Pre-dose) and Up to Week 24 ]
    EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. A global health status/QoL scale had total 2 items. Each global health status/QoL scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 6*100). The global health status/QoL scales range in score from 0 to 100. Higher score represents a higher ("better") level of health status/QoL. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30 [ Time Frame: Baseline (Day 1, Pre-dose) and Up to Week 24 ]
    EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale, and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Symptom scale had total 7 items (fatigue-3, pain-2, nausea/vomiting-2). Each symptoms scales and 6 single additional symptoms items score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales and 6 single additional symptoms scales range in score from 0 to 100. Higher score represents a higher ("worse") level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer Module (EORTC-QLQ-OV28) [ Time Frame: Baseline (Day 1, Pre-dose) and Up to 34 months ]
    EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/gastrointestinal [GI] symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Functional scales score (body Image and attitude to disease/treatment) was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). Functional scales score (sexuality) was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher ("better") level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
  • Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28 [ Time Frame: Baseline (Day 1, Pre-dose) and Up to 34 months ]
    EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/GI symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Symptoms scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales range in score from 0 to 100. Higher score represents a higher ("worse") level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
  • Overall Survival [ Time Frame: 36 months ]
    From date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
  • Safety and tolerability of Niraparib versus Placebo as Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: Approximately 36 months ]
    From date of screening until the date of study discontinuation or date of death from any cause, whichever came first
  • Patient Reported Outcomes (PROs) [ Time Frame: PROs are administered from screening until 12 weeks post study discontinuation or death from any cause. Approximately 36 months ]
  • Time to progression on the next anticancer therapy (PFS2) [ Time Frame: Approximately 36 months ]
    From date of start of next anticancer therapy to date of first documented progression of date of death from any cause, whichever comes first.
Current Other Pre-specified Outcome Measures
 (submitted: June 8, 2020)
  • Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE [ Time Frame: Up to 34 months ]
    An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
  • Area Under the Curve (AUC) From 0 to the Last Quantifiable Concentration (AUC[0-last]) [ Time Frame: Up to 34 months ]
    Blood samples were planned to be collected for assessment of AUC(0-last).
  • Peak Plasma Concentration (Cmax) [ Time Frame: Up to 34 months ]
    Blood samples were planned to be collected for assessment of Cmax.
  • Number of Participants With Positive HRD Test [ Time Frame: Up to 34 months ]
    Number of participants with positive HRD test was planned to be assessed.
Original Other Pre-specified Outcome Measures
 (submitted: January 12, 2016)
  • AUC0-last [ Time Frame: Up to 32 weeks ]
    AUC Area Under the Curve, time from 0 to the last quantifiable concentration
  • AUC [ Time Frame: Up to 32 weeks ]
    AUC Area Under the Curve, time from 0 to the last quantifiable concentration
  • Peak Plasma Concentration (Cmax) [ Time Frame: Up to 32 weeks ]
    Cmax Observed maximum plasma concentration
  • BRCA Diagnostic Test [ Time Frame: Samples for BRCA and HRD diagnostic testing will be obtained at screening and tested during the study. Additional biomarkers may be tested from an optional tumor sample if available at study treatment discontinuation, approximately 56months. ]
  • HRD Diagnostic Test [ Time Frame: Samples for BRCA and HRD diagnostic testing will be obtained at screening and tested during the study. Additional biomarkers may be tested from an optional tumor sample if available at study treatment discontinuation, approximately 56 months ]
 
Descriptive Information
Brief Title  ICMJE A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Brief Summary This study is a double-blind, randomized, placebo-controlled (2:1 niraparib:placebo) study in patients with Stage III or IV ovarian cancer. Patients must have completed front-line platinum based regimen with a physician-assessed response of Complete Response (CR) or Partial Response (PR). Additionally, patients must have a normal or >90% decrease in cancer antigen 125 (CA-125) following front-line platinum treatment. The study will assess the efficacy of niraparib as maintenance treatment, as measured by PFS.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Neoplasms
  • Ovarian Cancer
Intervention  ICMJE
  • Drug: Niraparib
    Niraparib vs Placebo 2:1 ratio
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Niraparib
    Administered once daily continuously during a 28 day cycle.
    Intervention: Drug: Niraparib
  • Placebo Comparator: Placebo
    Administered once daily continuously over a 28 day cycle
    Intervention: Drug: Placebo
Publications * González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 8, 2020)
733
Original Estimated Enrollment  ICMJE
 (submitted: January 12, 2016)
305
Estimated Study Completion Date  ICMJE March 29, 2024
Actual Primary Completion Date May 17, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • Patient must have histologically confirmed, advanced (FIGO Stage III or IV) high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have completed first line platinum based chemotherapy (neoadjuvant or adjuvant)
  • Patient must have clinical complete response or partial response following completion of chemotherapy course.
  • All Stage IV patients are eligible, irrespective of residual disease, after primary or interval debulking. Stage III patients are required to have visible residual disease after primary surgery. Patients with inoperable Stage III and IV disease are eligible
  • Patient must agree to undergo central tumor HRD testing
  • Patients of childbearing potential must have negative pregnancy serum test within 72 hours of being dosed
  • Patient must be randomized within 12 weeks of the first day of the last cycle of chemotherapy

Main Exclusion Criteria:

  • Patient has mucinous or clear cell subtypes of epithelial ovarian cancer, carcinosarcoma or undifferentiated ovarian cancer
  • Patient has undergone more than 2 debulking surgeries
  • Patient is to receive bevacizumab as maintenance treatment
  • Patient is pregnant, breastfeeding, or expecting to conceive children, while receiving study treatment and for 180 days after the last dose of study treatment
  • Patient has had prior treatment with a known PARP inhibitor
  • Patient has been diagnosed and/or treated for any invasive cancer (other than study disease) less than 5 years prior to study enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02655016
Other Study ID Numbers  ICMJE 213359
PR-30-5017-C ( Other Identifier: Tesaro )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE
  • Gynecologic Oncology Group
  • European Network of Gynaecological Oncological Trial Groups (ENGOT)
  • Myriad Genetics, Inc.
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Tesaro, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP