A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA)

A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

This is a Phase 2, open-label, single arm study to evaluate the safety and efficacy of niraparib in ovarian cancer patients who have received three or four previous chemotherapy regimens. Niraparib is an orally active PARP inhibitor. Niraparib will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by Eastern Cooperative Oncology Group performance status (ECOG). Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), RECIST tumor assessments and safety laboratory values.

Study Overview

• Status: Completed
• Conditions: Ovarian Neoplasms; Ovarian Cancer
• Intervention / Treatment: Drug: Niraparib

• Study Type: Interventional
• Enrollment (Actual): 463
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • GSK Investigational Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H1T 2M4
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H2L 4M1
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H4A 3J1
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • GSK Investigational Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85016
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85710
      • GSK Investigational Site
  • California
    • Burbank, California, United States, 91505
      • GSK Investigational Site
    • Duarte, California, United States, 91010
      • GSK Investigational Site
    • Los Angeles, California, United States, 90027
      • GSK Investigational Site
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
    • San Francisco, California, United States, 94118
      • GSK Investigational Site
    • Santa Barbara, California, United States, 93105
      • GSK Investigational Site
    • Stanford, California, United States, 94305-5317
      • GSK Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • GSK Investigational Site
  • Florida
    • Tampa, Florida, United States, 33612
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • GSK Investigational Site
    • Chicago, Illinois, United States, 60611
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • GSK Investigational Site
    • Indianapolis, Indiana, United States, 54244
      • GSK Investigational Site
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • GSK Investigational Site
    • New Orleans, Louisiana, United States, 70121
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • GSK Investigational Site
    • Boston, Massachusetts, United States, 02115
      • GSK Investigational Site
    • Burlington, Massachusetts, United States, 01805
      • GSK Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • GSK Investigational Site
    • Rochester, Minnesota, United States, 55905
      • GSK Investigational Site
  • Missouri
    • Springfield, Missouri, United States, 65804
      • GSK Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • GSK Investigational Site
    • Morristown, New Jersey, United States, 07962-1956
      • GSK Investigational Site
  • New York
    • East Setauket, New York, United States, 11733
      • GSK Investigational Site
    • Jamaica, New York, United States, 11432
      • GSK Investigational Site
    • Lake Success, New York, United States, 11042
      • GSK Investigational Site
    • New York, New York, United States, 10065
      • GSK Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504-8342
      • GSK Investigational Site
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • GSK Investigational Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • GSK Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • GSK Investigational Site
    • Dallas, Texas, United States, 75390
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76104
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • The Woodlands, Texas, United States, 77380
      • GSK Investigational Site
    • Tyler, Texas, United States, 75702
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • GSK Investigational Site
    • Tacoma, Washington, United States, 98405
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must agree to undergo tumor HRD testing and blood gBRCAmut status testing.
• Patients of childbearing potential must have negative pregnancy serum test within 72 hours of being dosed
• Patients must have histologically diagnosed high-grade (Grade 2 or 3) serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent disease and must have been previously treated with chemotherapy and experienced a response lasting at least 6 months to first-line platinum based therapy.
• Patients Must have completed 3 or 4 previous chemotherapy regimens.
• Patients must have completed their last chemotherapy regimen > 4 weeks prior to treatment initiation.
• Patients must have measurable disease according to RECIST (v.1.1).
• Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.
• Patients must agree to blood samples during screening and at the end of treatment for cytogenetic analysis.

Exclusion Criteria:

• Patients must not have any known, persistent (> 4 weeks), ≥Grade 3 hematologic toxicity during the last cancer therapy. Patients must not have any known, persistent (>4 weeks), ≥ Grade 3 fatigue during the last cancer therapy.
• Patients must not have received pelvic radiotherapy as treatment for primary or recurrent disease within 1 year of the first dose of study treatment.
• Patients must not have symptomatic uncontrolled brain or leptomeningeal metastases.
• Patients must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection.
• Patients must not have received a transfusion (platelets or red blood cells) within 4 weeks of the first dose of study treatment.
• Patients must not have known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Niraparib	Drug: Niraparib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis, PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	DoR was defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by the Investigator per RECIST (version1.1). DoR was analyzed using Kaplan-Meier (KM) method.	Up to 3 years
ORR by HRD Status and Breast Cancer Gene (BRCA) Status	The ORR was defined as the percentage of participants achieving CR or PR as assessed by the Investigator per RECIST (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. ORR was evaluated for participants with following characteristics: HRD status (positive, negative and unknown) and BRCA status (mutation positive, wild-type and unknown).	Up to 3 years
Disease Control Rate (DCR)	Disease control rate was defined as the percentage of participants achieving CR, PR, or stable disease (SD) as assessed by the Investigator per RECIST (version1.1). The exact (Clopper-Pearson) method was used to calculate 95% confidence interval.	Up to 3 years
Progression Free Survival	Progression-free survival was defined as the time from the date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression as assessed by the Investigator per RECIST (version 1.1) or clinical criteria. Progression is defined using RECIST version1.1 as at least a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.	Up to 3 years
Overall Survival	Overall Survival was defined as the time from the date of the first dose to the date of death by any cause. It was calculated as (Date of Death minus First dose date plus 1) divided by 30.4375.	Up to 3 years
Time to First Subsequent Therapy (TFST)	Time to first subsequent therapy (TFST) was defined as the time from the date of first dose to the date of first subsequent therapy or death, whichever occurs first. It was calculated as (Earlier of [First dose of first subsequent therapy or death] minus First dose date plus 1) divided by 30.4375.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Non-serious Adverse Event (Non-SAE) and Any Serious Adverse Event (SAE)	An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Adverse events which were not serious were considered as Non-serious adverse events.	Up to a maximum of 71.56 months
Number of Participants With Abnormality in Hematology Parameters	Number of participants with abnormality in hematology parameters were planned to be analyzed.	Up to 3 years
Number of Participants With Abnormality in Clinical Chemistry Parameters	Number of participants with abnormality in clinical chemistry parameters were planned to be analyzed.	Up to 3 years
Number of Participants With Abnormality in Vital Signs	Number of participants with abnormality in vital signs were planned to be analyzed.	Up to 3 years
Number of Participants With Abnormality in Physical Examination	Number of participants with abnormality in physical examination were planned to be analyzed.	Up to 3 years
Number of Participants Who Were Administered Concomitant Medications	Number of participants who were administered concomitant medications were planned to be analyzed.	Up to 3 years

Collaborators and Investigators

• Sponsor: Tesaro, Inc.
• Collaborators: Myriad Genetics, Inc.; Facing Our Risk of Cancer Empowered

Publications and helpful links

General Publications

• Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4. Epub 2019 Apr 1. Erratum In: Lancet Oncol. 2019 May;20(5):e242.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 23, 2015
• Primary Completion (ACTUAL): February 28, 2018
• Study Completion (ACTUAL): August 23, 2021

Study Registration Dates

• First Submitted: January 23, 2015
• First Submitted That Met QC Criteria: January 29, 2015
• First Posted (ESTIMATE): February 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: August 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: PARP inhibitor; Ovarian cancer; BRCA; Primary Peritoneal; Fallopian Tube; HRD; gBRCAmut; Serous Epithelial
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: 213360; PR-30-5020-C (OTHER: Tesaro)