Clinical trial NCT02354586: A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Ovarian Cancer
Keywords: gBRCAmut
BRCA
PARP inhibitor
HRD
Ovarian cancer
Serous Epithelial
Fallopian Tube
Primary Peritoneal
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Facing Our Risk of Cancer Empowered
name: Myriad Genetics, Inc.
First posted: 2015-02-03
Enrollment: 463
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Duration of Response (DoR)
timeFrame: Up to 3 years
measure: ORR by HRD Status and Breast Cancer Gene (BRCA) Status
timeFrame: Up to 3 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 3 years
measure: Progression Free Survival
timeFrame: Up to 3 years
measure: Overall Survival
timeFrame: Up to 3 years
measure: Time to First Subsequent Therapy (TFST)
timeFrame: Up to 3 years
Other outcomes:
measure: Number of Participants With Any Non-serious Adverse Event (Non-SAE) and Any Serious Adverse Event (SAE)
timeFrame: Up to a maximum of 71.56 months
measure: Number of Participants With Abnormality in Hematology Parameters
timeFrame: Up to 3 years
measure: Number of Participants With Abnormality in Clinical Chemistry Parameters
timeFrame: Up to 3 years
measure: Number of Participants With Abnormality in Vital Signs
timeFrame: Up to 3 years
measure: Number of Participants With Abnormality in Physical Examination
timeFrame: Up to 3 years
measure: Number of Participants Who Were Administered Concomitant Medications
timeFrame: Up to 3 years
Locations:
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Burbank
country: United States
facility: GSK Investigational Site
state: California
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Santa Barbara
country: United States
facility: GSK Investigational Site
state: California
city: Stanford
country: United States
facility: GSK Investigational Site
state: California
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Covington
country: United States
facility: GSK Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Burlington
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Hackensack
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Morristown
country: United States
facility: GSK Investigational Site
state: New Jersey
city: East Setauket
country: United States
facility: GSK Investigational Site
state: New York
city: Jamaica
country: United States
facility: GSK Investigational Site
state: New York
city: Lake Success
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Wynnewood
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: The Woodlands
country: United States
facility: GSK Investigational Site
state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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.