Clinical trial NCT01905592: A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
Official title: A Phase III, Randomized, Open Label, Multicenter, Controlled Trial of Niraparib Versus Physician's Choice in Previously-treated, HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neoplasms, Breast
Carcinoma of Breast
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
BRCA1 Gene Mutation
BRCA2 Gene Mutation
Ovarian Neoplasms
Keywords: Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
BRCA1 Gene Mutation
BRCA2 Gene Mutation
PARP Inhibitor
BRCA
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: Breast International Group
name: Myriad Genetic Laboratories, Inc.
name: US Oncology Research
name: Sarah Cannon
name: Facing Our Risk of Cancer Empowered
First posted: 2013-07-23
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare progression-free survival (PFS) in patients with advanced/metastatic breast cancer who have a BRCA mutation when treated with niraparib as compared to those treated with physician's choice

Detailed description: This is a phase III, randomized, open label, multicenter, controlled trial of niraparib versus physician's choice in previously-treated, HER2 negative, germline BRCA mutation-positive breast cancer patients. Niraparib is an orally active PARP inhibitor. Niraparib (in a 2:1 ratio) will be administered once daily continuously during a 21-day cycle. Physician's choice will be administered on a 21-day cycle. Health-related quality of life will be measured. The safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

Eligibility criteria: Inclusion Criteria:

1. Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
2. Histologically or cytologically confirmed HER2-negative metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
3. Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer; patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy.
4. Prior therapy should have included a taxane and/or anthracycline (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting.

   a. Hormone receptor positive patients must also have hormone resistant disease; either relapsed while on adjuvant endocrine treatment, or within one year of completing adjuvant endocrine treatment, or progression on at least one line of endocrine treatment for advanced cancer.
5. ECOG performance status 0-2
6. Adequate bone marrow, kidney and liver function

Exclusion Criteria:

1. Patients with platinum resistant cancer
2. Symptomatic uncontrolled brain metastases
3. Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval; Stage II ovarian cancer must have a 2-year disease-free interval
4. Known hypersensitivity to the components of niraparib
5. Invasive cancer other than breast cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
6. Pregnant or breast feeding patients
7. Immunocompromised patients
8. Known active Hepatitis B or C
9. Prior treatment with a PARP inhibitor
10. Known history of myelodysplastic syndrome (MDS).
11. known and persistent (\>4 weeks) \>/= grade 3 toxicity or fatigue from prior cancer treatment.

Primary outcomes:
measure: Progression Free Survival (PFS) - Central Review Assessment
timeFrame: From the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier, up to 4 years
Secondary outcomes:
measure: Overall Survival
timeFrame: From treatment randomization to date of death of any cause, up to 4 years
measure: Number of Participants With Central BRCA Mutation Status
timeFrame: At Baseline (Cycle 1 Day1) (Cycle duration was 21 days)
measure: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
timeFrame: Up to 7 years
measure: Progression Free Survival (PFS) - Investigator Assessment
timeFrame: Assessed up to 4 years
measure: Time to Treatment Failure
timeFrame: Date of randomization to discontinuation of treatment for any reason, up to 4 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Number of Participants With Serious Adverse Events Related to New Malignancy
timeFrame: Up to 7 years
measure: Number of Participants With Subsequent Anticancer Therapies
timeFrame: Up to 7 years
Other outcomes:
measure: Number of Participants With Minimally Clinically Important Difference (MCID) Status in European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)
timeFrame: Up to 7 years
measure: Number of Participants With Euroqol 5 Dimension 5 Level (EQ-5D-5L) Dimension Scores by Visit
timeFrame: Up to 7 years
measure: Number of Participants With Any Subsequent Therapies Post Discontinuation of Study Treatment and Association With Potential Survival Related Outcomes
timeFrame: Up to 7 years
measure: Number of Participants With Presence of Genetic and Non-genetic Biomarkers
timeFrame: Up to 7 years
measure: Number of Participants With Germline BRCA1 and BRCA2 Mutation Status in Association With Survival Related Outcomes
timeFrame: Up to 7 years
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
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: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Clifton Park
country: United States
facility: GSK Investigational Site
state: New York
city: Lake Success
country: United States
facility: GSK Investigational Site
state: New York
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Eugene
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
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: Webster
country: United States
facility: GSK Investigational Site
state: Texas
city: Weslaco
country: United States
facility: GSK Investigational Site
state: Texas
city: Low Moor
country: United States
facility: GSK Investigational Site
state: Virginia
city: Everett
country: United States
facility: GSK Investigational Site
state: Washington
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Green Bay
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Aalst
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Namur
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Dijon Cedex
country: France
facility: GSK Investigational Site
city: Lille Cedex
country: France
facility: GSK Investigational Site
city: Lyon Cedex 08
country: France
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Nantes cedex
country: France
facility: GSK Investigational Site
city: Paris Cedex 5
country: France
facility: GSK Investigational Site
city: Saint-Cloud
country: France
facility: GSK Investigational Site
city: Heraklion,Crete
country: Greece
facility: GSK Investigational Site
city: Maroussi
country: Greece
facility: GSK Investigational Site
city: Nea Kifissia
country: Greece
facility: GSK Investigational Site
city: Neo Faliro
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Miskolc
country: Hungary
facility: GSK Investigational Site
city: Nyiregyhaza
country: Hungary
facility: GSK Investigational Site
city: Pécs
country: Hungary
facility: GSK Investigational Site
city: Szeged
country: Hungary
facility: GSK Investigational Site
city: Reykjavik
country: Iceland
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Holon
country: Israel
facility: GSK Investigational Site
city: Kfar-Saba
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Tel Hashomer
country: Israel
facility: GSK Investigational Site
city: Meldola (FC)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Parma
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Viterbo
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Cremona
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Ancona
country: Italy
facility: GSK Investigational Site
state: Marche
city: Lecce
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Prato
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Legnago (VR)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Leiden, RC
country: Netherlands
facility: GSK Investigational Site
city: Limburg
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Raciborz
country: Poland
facility: GSK Investigational Site
city: Coimbra
country: Portugal
facility: GSK Investigational Site
city: Lisbon
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Cáceres
country: Spain
facility: GSK Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: GSK Investigational Site
city: Lerida
country: Spain
facility: GSK Investigational Site
city: Lugo
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo
country: Spain
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
state: Hampshire
city: Northwood
country: United Kingdom
facility: GSK Investigational Site
state: Middlesex
city: Headington, Oxford
country: United Kingdom
facility: GSK Investigational Site
state: Oxfordshire
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
state: Surrey
city: Bebington, Wirral
country: United Kingdom
facility: GSK Investigational Site
city: Belfast
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Whitchurch, Cardiff
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: