A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients

NCT01905592 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: 2135511307-BCG, BIG5-13PR-30-5010-C
• Study Type: interventional
• Target: 216
• Locations: 14 countries
• Sites: 104

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

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) - Central Review Assessment

  The primary objective of this study is to compare progression-free survival (PFS), as assessed by blinded central review, of participants with advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gBRCA mutation breast cancer when treated with niraparib as compared to those treated with physician's choice single agent chemotherapy standards (eribulin, vinorelbine, gemcitabine or capecitabine). PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by central review assessment. Progressive Disease is defined as at least a 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 millimeter (mm).

  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 (9)

• Overall Survival

  From treatment randomization to date of death of any cause, up to 4 years

• Number of Participants With Central BRCA Mutation Status

  At Baseline (Cycle 1 Day1) (Cycle duration was 21 days)

• Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)

  Up to 7 years

• Progression Free Survival (PFS) - Investigator Assessment

  Assessed up to 4 years

• Time to Treatment Failure

  Date of randomization to discontinuation of treatment for any reason, up to 4 years

Other Outcomes (5)

• 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)

  Up to 7 years

• Number of Participants With Euroqol 5 Dimension 5 Level (EQ-5D-5L) Dimension Scores by Visit

  Up to 7 years

• Number of Participants With Any Subsequent Therapies Post Discontinuation of Study Treatment and Association With Potential Survival Related Outcomes

  Up to 7 years

Study Arms (2)

Physician's choice

ACTIVE COMPARATOR

Physician may select from 4 active comparators

Drug: Physician's choice

niraparib

EXPERIMENTAL

Patients will be randomized 2:1 to receive niraparib 300 mg (3x100 mg capsules) once daily for 21 continuous days

Drug: niraparib

Interventions

niraparib DRUG

300 mg (3x100 mg capsules) once daily until progression or unacceptable toxicity develops

Also known as: formerly MK-4827

niraparib

Physician's choice DRUG

Choice of 4 standard of care metastatic breast cancer chemotherapies, until progression or unacceptable toxicity develops

Physician's choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation.
• Histologically or cytologically confirmed HER2-negative metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
• 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.
• 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.
• ECOG performance status 0-2
• Adequate bone marrow, kidney and liver function

You may not qualify if:

• Patients with platinum resistant cancer
• Symptomatic uncontrolled brain metastases
• 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
• Known hypersensitivity to the components of niraparib
• Invasive cancer other than breast cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
• Pregnant or breast feeding patients
• Immunocompromised patients
• Known active Hepatitis B or C
• Prior treatment with a PARP inhibitor
• Known history of myelodysplastic syndrome (MDS).
• known and persistent (\>4 weeks) \>/= grade 3 toxicity or fatigue from prior cancer treatment.

Sponsors & Collaborators

• Tesaro, Inc.: lead
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• Breast International Group: collaborator
• Myriad Genetic Laboratories, Inc.: collaborator
• US Oncology Research: collaborator
• Sarah Cannon: collaborator
• Facing Our Risk of Cancer Empowered: collaborator

Study Sites (104)

GSK Investigational Site

Tucson, Arizona, 85710, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Los Angeles, California, 90048, United States

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GSK Investigational Site

Fort Myers, Florida, 33901, United States

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GSK Investigational Site

Miami, Florida, 33176, United States

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GSK Investigational Site

Boston, Massachusetts, 02111, United States

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GSK Investigational Site

Omaha, Nebraska, 68114, United States

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GSK Investigational Site

Henderson, Nevada, 89074, United States

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GSK Investigational Site

Clifton Park, New York, 12065, United States

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GSK Investigational Site

Lake Success, New York, 11042, United States

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GSK Investigational Site

Cleveland, Ohio, 44195, United States

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GSK Investigational Site

Eugene, Oregon, 97401, United States

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GSK Investigational Site

Portland, Oregon, 97225, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

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GSK Investigational Site

Nashville, Tennessee, 37203, United States

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GSK Investigational Site

Nashville, Tennessee, 37232, United States

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GSK Investigational Site

Dallas, Texas, 75237, United States

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GSK Investigational Site

Fort Worth, Texas, 76104, United States

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GSK Investigational Site

San Antonio, Texas, 78217, United States

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GSK Investigational Site

Webster, Texas, 77598, United States

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GSK Investigational Site

Weslaco, Texas, 78596, United States

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GSK Investigational Site

Low Moor, Virginia, 24457, United States

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GSK Investigational Site

Everett, Washington, 98201, United States

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GSK Investigational Site

Seattle, Washington, 98111, United States

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GSK Investigational Site

Green Bay, Wisconsin, 54311, United States

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GSK Investigational Site

Aalst, 9300, Belgium

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Brussels, 1200, Belgium

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GSK Investigational Site

Edegem, 2650, Belgium

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GSK Investigational Site

Liège, 4000, Belgium

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GSK Investigational Site

Namur, 5000, Belgium

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GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

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GSK Investigational Site

Kelowna, British Columbia, V1Y 5L3, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4M1, Canada

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GSK Investigational Site

Bordeaux, 33076, France

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GSK Investigational Site

Dijon, 21079, France

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GSK Investigational Site

Lille, 59020, France

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GSK Investigational Site

Lyon, 69373, France

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GSK Investigational Site

Montpellier, 34298, France

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GSK Investigational Site

Nantes, 44202, France

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GSK Investigational Site

Paris, 75248, France

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GSK Investigational Site

Saint-Cloud, 92210, France

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GSK Investigational Site

Heraklion,Crete, 71110, Greece

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GSK Investigational Site

Marousi, 15123, Greece

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GSK Investigational Site

Nea Kifissia, 14564, Greece

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GSK Investigational Site

Neo Faliro, 18547, Greece

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GSK Investigational Site

Thessaloniki, 57001, Greece

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GSK Investigational Site

Budapest, 1122, Hungary

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GSK Investigational Site

Debrecen, 4032, Hungary

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GSK Investigational Site

Miskolc, 3501, Hungary

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GSK Investigational Site

Nyíregyháza, 4400, Hungary

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GSK Investigational Site

Pécs, 7624, Hungary

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GSK Investigational Site

Szeged, 6720, Hungary

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GSK Investigational Site

Reykjavik, IS-101, Iceland

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GSK Investigational Site

Haifa, 3109601, Israel

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GSK Investigational Site

Holon, 58100, Israel

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GSK Investigational Site

Kfar Saba, 44281, Israel

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GSK Investigational Site

Rehovot, 76100, Israel

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GSK Investigational Site

Tel Aviv, 6423906, Israel

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GSK Investigational Site

Tel Litwinsky, 52621, Israel

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GSK Investigational Site

Lecce, Apulia, 73100, Italy

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GSK Investigational Site

Meldola (FC), Emilia-Romagna, 47014, Italy

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GSK Investigational Site

Parma, Emilia-Romagna, 43100, Italy

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GSK Investigational Site

Rimini, Emilia-Romagna, 47900, Italy

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GSK Investigational Site

Viterbo, Lazio, 01100, Italy

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GSK Investigational Site

Genoa, Liguria, 16132, Italy

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GSK Investigational Site

Cremona, Lombardy, 26100, Italy

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GSK Investigational Site

Milan, Lombardy, 20141, Italy

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GSK Investigational Site

Ancona, The Marches, 60020, Italy

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GSK Investigational Site

Prato, Tuscany, 59100, Italy

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GSK Investigational Site

Legnago (VR), Veneto, 37045, Italy

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GSK Investigational Site

Leiden, RC, 2333 ZA, Netherlands

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GSK Investigational Site

Limburg, 6229HX, Netherlands

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GSK Investigational Site

Zwolle, 8025 AB, Netherlands

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GSK Investigational Site

Lodz, 93-513, Poland

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GSK Investigational Site

Racibórz, 47-400, Poland

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GSK Investigational Site

Coimbra, 3000-075, Portugal

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GSK Investigational Site

Lisbon, 1400-038, Portugal

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GSK Investigational Site

Porto, 4200-072, Portugal

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GSK Investigational Site

Barcelona, 8035, Spain

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GSK Investigational Site

Burgos, 09005, Spain

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GSK Investigational Site

Cáceres, 10003, Spain

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GSK Investigational Site

L'Hospitalet de Llobregat, 8907, Spain

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GSK Investigational Site

Lleida, 25198, Spain

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GSK Investigational Site

Lugo, 27003, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Pamplona, 31008, Spain

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GSK Investigational Site

Valencia, 46009, Spain

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GSK Investigational Site

Valencia, 46015, Spain

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GSK Investigational Site

Vigo, 36312, Spain

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GSK Investigational Site

Southampton, Hampshire, SO16 6YD, United Kingdom

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GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

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GSK Investigational Site

Headington, Oxford, Oxfordshire, OX3 7LJ, United Kingdom

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GSK Investigational Site

Sutton, Surrey, SM2 5PT, United Kingdom

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GSK Investigational Site

Bebington, Wirral, CH63 4JY, United Kingdom

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GSK Investigational Site

Belfast, BT9 7AB, United Kingdom

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GSK Investigational Site

Edinburgh, EH4 2XU, United Kingdom

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GSK Investigational Site

Glasgow, G11 6NT, United Kingdom

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GSK Investigational Site

London, NW1 2PG, United Kingdom

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GSK Investigational Site

London, SE1 9RT, United Kingdom

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GSK Investigational Site

London, SW3 6JJ, United Kingdom

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GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

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GSK Investigational Site

Whitchurch, Cardiff, CF14 2TL, United Kingdom

Location

Related Links

• Facing our risk of cancer empowered website

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Limitations and Caveats

IDMC interim analysis concluded that concerns with the quantity and quality of data in the control arm precluded meaningful comparative analyses and generation of a clinically useful endpoint, therefore enrollment was ended prematurely.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations.

Study Record Dates

• First Submitted: July 18, 2013
• First Posted: July 23, 2013
• Study Start: February 25, 2014
• Primary Completion: May 23, 2018
• Study Completion: October 26, 2021
• Last Updated: November 15, 2022
• Results First Posted: August 27, 2020

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (13); IC (1); PL (2); US (25); GR (5); HU (6); CA (4); IL (6); BE (6); IT (11); NL (3); FR (8); ES (11); PT (3)