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

Ovarian Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02354586
• Other study ID #: 213360
• Secondary ID: PR-30-5020-C
• Status: Completed
• Phase: Phase 2
• Start date: March 23, 2015
• Est. completion date: August 23, 2021

Study information

• Verified date: July 2022
• Source: Tesaro, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: August 23, 2021
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Niraparib

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Burbank	California
United States	GSK Investigational Site	Burlington	Massachusetts
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Covington	Louisiana
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Duarte	California
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	East Setauket	New York
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Hackensack	New Jersey
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jamaica	New York
United States	GSK Investigational Site	Lake Success	New York
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Morristown	New Jersey
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Santa Barbara	California
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Springfield	Missouri
United States	GSK Investigational Site	Stanford	California
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	The Woodlands	Texas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tyler	Texas
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Wynnewood	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Tesaro, Inc.	Facing Our Risk of Cancer Empowered, Myriad Genetics, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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