search
Back to results

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

Primary Purpose

Ovarian Neoplasms, Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Niraparib
Sponsored by
Tesaro, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Neoplasms focused on measuring gBRCAmut, BRCA, PARP inhibitor, HRD, Ovarian cancer, Serous Epithelial, Fallopian Tube, Primary Peritoneal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Niraparib

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.

Full Information

First Posted
January 23, 2015
Last Updated
August 21, 2022
Sponsor
Tesaro, Inc.
Collaborators
Facing Our Risk of Cancer Empowered, Myriad Genetics, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02354586
Brief Title
A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens
Acronym
QUADRA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
March 23, 2015 (Actual)
Primary Completion Date
February 28, 2018 (Actual)
Study Completion Date
August 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tesaro, Inc.
Collaborators
Facing Our Risk of Cancer Empowered, Myriad Genetics, Inc.

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms, Ovarian Cancer
Keywords
gBRCAmut, BRCA, PARP inhibitor, HRD, Ovarian cancer, Serous Epithelial, Fallopian Tube, Primary Peritoneal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
463 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Niraparib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Niraparib
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Duration of Response (DoR)
Description
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.
Time Frame
Up to 3 years
Title
ORR by HRD Status and Breast Cancer Gene (BRCA) Status
Description
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).
Time Frame
Up to 3 years
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
Up to 3 years
Title
Progression Free Survival
Description
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.
Time Frame
Up to 3 years
Title
Overall Survival
Description
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.
Time Frame
Up to 3 years
Title
Time to First Subsequent Therapy (TFST)
Description
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.
Time Frame
Up to 3 years
Other Pre-specified Outcome Measures:
Title
Number of Participants With Any Non-serious Adverse Event (Non-SAE) and Any Serious Adverse Event (SAE)
Description
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.
Time Frame
Up to a maximum of 71.56 months
Title
Number of Participants With Abnormality in Hematology Parameters
Description
Number of participants with abnormality in hematology parameters were planned to be analyzed.
Time Frame
Up to 3 years
Title
Number of Participants With Abnormality in Clinical Chemistry Parameters
Description
Number of participants with abnormality in clinical chemistry parameters were planned to be analyzed.
Time Frame
Up to 3 years
Title
Number of Participants With Abnormality in Vital Signs
Description
Number of participants with abnormality in vital signs were planned to be analyzed.
Time Frame
Up to 3 years
Title
Number of Participants With Abnormality in Physical Examination
Description
Number of participants with abnormality in physical examination were planned to be analyzed.
Time Frame
Up to 3 years
Title
Number of Participants Who Were Administered Concomitant Medications
Description
Number of participants who were administered concomitant medications were planned to be analyzed.
Time Frame
Up to 3 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
GSK Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
Facility Name
GSK Investigational Site
City
Burbank
State/Province
California
ZIP/Postal Code
91505
Country
United States
Facility Name
GSK Investigational Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
GSK Investigational Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Facility Name
GSK Investigational Site
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
GSK Investigational Site
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5317
Country
United States
Facility Name
GSK Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
GSK Investigational Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
GSK Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
GSK Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
GSK Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
54244
Country
United States
Facility Name
GSK Investigational Site
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
GSK Investigational Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
GSK Investigational Site
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
GSK Investigational Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
GSK Investigational Site
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
GSK Investigational Site
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
GSK Investigational Site
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962-1956
Country
United States
Facility Name
GSK Investigational Site
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
GSK Investigational Site
City
Jamaica
State/Province
New York
ZIP/Postal Code
11432
Country
United States
Facility Name
GSK Investigational Site
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
GSK Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
GSK Investigational Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
GSK Investigational Site
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504-8342
Country
United States
Facility Name
GSK Investigational Site
City
Wynnewood
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
Facility Name
GSK Investigational Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
GSK Investigational Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
GSK Investigational Site
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77380
Country
United States
Facility Name
GSK Investigational Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
GSK Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
GSK Investigational Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
GSK Investigational Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
GSK Investigational Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
30948273
Citation
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs