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Neoplasms, BreastPhase 3BRAVONCT01905592

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

A Phase 3 study testing niraparib and Physician's choice in people with Neoplasms, Breast and Carcinoma of Breast, run by Tesaro, Inc. at 104 sites in 14 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
niraparib and Physician's choice
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
216 participants
Where
104 sitesin 14 countries
Study dates
25 Feb 2014to 26 Oct 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

104 sites in 14 countries.

104 sites in 14 countries

United States25 sites

  • GSK Investigational Site

    Boston, Massachusetts, 02111

  • GSK Investigational Site

    Cleveland, Ohio, 44195

  • GSK Investigational Site

    Clifton Park, New York, 12065

  • GSK Investigational Site

    Dallas, Texas, 75237

  • GSK Investigational Site

    Eugene, Oregon, 97401

  • GSK Investigational Site

    Everett, Washington, 98201

  • GSK Investigational Site

    Fort Myers, Florida, 33901

  • GSK Investigational Site

    Fort Worth, Texas, 76104

  • GSK Investigational Site

    Green Bay, Wisconsin, 54311

  • GSK Investigational Site

    Henderson, Nevada, 89074

  • GSK Investigational Site

    Lake Success, New York, 11042

  • GSK Investigational Site

    Los Angeles, California, 90033

  • GSK Investigational Site

    Los Angeles, California, 90048

  • GSK Investigational Site

    Low Moor, Virginia, 24457

  • GSK Investigational Site

    Miami, Florida, 33176

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    Nashville, Tennessee, 37232

  • GSK Investigational Site

    Omaha, Nebraska, 68114

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19111

  • GSK Investigational Site

    Portland, Oregon, 97225

  • GSK Investigational Site

    San Antonio, Texas, 78217

  • GSK Investigational Site

    Seattle, Washington, 98111

  • GSK Investigational Site

    Tucson, Arizona, 85710

  • GSK Investigational Site

    Webster, Texas, 77598

  • GSK Investigational Site

    Weslaco, Texas, 78596

Other trials in United States

United Kingdom13 sites

  • GSK Investigational Site

    Bebington, Wirral, CH63 4JY

  • GSK Investigational Site

    Belfast, BT9 7AB

  • GSK Investigational Site

    Edinburgh, EH4 2XU

  • GSK Investigational Site

    Glasgow, G11 6NT

  • GSK Investigational Site

    Headington, Oxford, Oxfordshire, OX3 7LJ

  • GSK Investigational Site

    London, NW1 2PG

  • GSK Investigational Site

    London, SE1 9RT

  • GSK Investigational Site

    London, SW3 6JJ

  • GSK Investigational Site

    Northwood, Middlesex, HA6 2RN

  • GSK Investigational Site

    Nottingham, NG5 1PB

  • GSK Investigational Site

    Southampton, Hampshire, SO16 6YD

  • GSK Investigational Site

    Sutton, Surrey, SM2 5PT

  • GSK Investigational Site

    Whitchurch, Cardiff, CF14 2TL

Other trials in United Kingdom

Italy11 sites

  • GSK Investigational Site

    Ancona, The Marches, 60020

  • GSK Investigational Site

    Cremona, Lombardy, 26100

  • GSK Investigational Site

    Genoa, Liguria, 16132

  • GSK Investigational Site

    Lecce, Apulia, 73100

  • GSK Investigational Site

    Legnago (VR), Veneto, 37045

  • GSK Investigational Site

    Meldola (FC), Emilia-Romagna, 47014

  • GSK Investigational Site

    Milan, Lombardy, 20141

  • GSK Investigational Site

    Parma, Emilia-Romagna, 43100

  • GSK Investigational Site

    Prato, Tuscany, 59100

  • GSK Investigational Site

    Rimini, Emilia-Romagna, 47900

  • GSK Investigational Site

    Viterbo, Lazio, 01100

Other trials in Italy

Spain11 sites

  • GSK Investigational Site

    Barcelona, 8035

  • GSK Investigational Site

    Burgos, 09005

  • GSK Investigational Site

    Cáceres, 10003

  • GSK Investigational Site

    L'Hospitalet de Llobregat, 8907

  • GSK Investigational Site

    Lleida, 25198

  • GSK Investigational Site

    Lugo, 27003

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Pamplona, 31008

  • GSK Investigational Site

    Valencia, 46009

  • GSK Investigational Site

    Valencia, 46015

  • GSK Investigational Site

    Vigo, 36312

Other trials in Spain

France8 sites

  • GSK Investigational Site

    Bordeaux, 33076

  • GSK Investigational Site

    Dijon, 21079

  • GSK Investigational Site

    Lille, 59020

  • GSK Investigational Site

    Lyon, 69373

  • GSK Investigational Site

    Montpellier, 34298

  • GSK Investigational Site

    Nantes, 44202

  • GSK Investigational Site

    Paris, 75248

  • GSK Investigational Site

    Saint-Cloud, 92210

Other trials in France

Belgium6 sites

  • GSK Investigational Site

    Aalst, 9300

  • GSK Investigational Site

    Brussels, 1000

  • GSK Investigational Site

    Brussels, 1200

  • GSK Investigational Site

    Edegem, 2650

  • GSK Investigational Site

    Liège, 4000

  • GSK Investigational Site

    Namur, 5000

Other trials in Belgium

Hungary6 sites

  • GSK Investigational Site

    Budapest, 1122

  • GSK Investigational Site

    Debrecen, 4032

  • GSK Investigational Site

    Miskolc, 3501

  • GSK Investigational Site

    Nyíregyháza, 4400

  • GSK Investigational Site

    Pécs, 7624

  • GSK Investigational Site

    Szeged, 6720

Other trials in Hungary

Israel6 sites

  • GSK Investigational Site

    Haifa, 3109601

  • GSK Investigational Site

    Holon, 58100

  • GSK Investigational Site

    Kfar Saba, 44281

  • GSK Investigational Site

    Rehovot, 76100

  • GSK Investigational Site

    Tel Aviv, 6423906

  • GSK Investigational Site

    Tel HaShomer, 52621

Other trials in Israel

Greece5 sites

  • GSK Investigational Site

    Heraklion,Crete, 71110

  • GSK Investigational Site

    Marousi, 15123

  • GSK Investigational Site

    Nea Kifissia, 14564

  • GSK Investigational Site

    Neo Faliro, 18547

  • GSK Investigational Site

    Thessaloniki, 57001

Other trials in Greece

Canada4 sites

  • GSK Investigational Site

    Calgary, Alberta, T2N 4N2

  • GSK Investigational Site

    Kelowna, British Columbia, V1Y 5L3

  • GSK Investigational Site

    Montreal, Quebec, H2L 4M1

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Netherlands3 sites

  • GSK Investigational Site

    Leiden, RC, 2333 ZA

  • GSK Investigational Site

    Limburg, 6229HX

  • GSK Investigational Site

    Zwolle, 8025 AB

Other trials in Netherlands

Portugal3 sites

  • GSK Investigational Site

    Coimbra, 3000-075

  • GSK Investigational Site

    Lisbon, 1400-038

  • GSK Investigational Site

    Porto, 4200-072

Other trials in Portugal

Poland2 sites

  • GSK Investigational Site

    Lodz, 93-513

  • GSK Investigational Site

    Racibórz, 47-400

Other trials in Poland

Iceland1 site

  • GSK Investigational Site

    Reykjavik, IS-101

Other trials in Iceland

About this study

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

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

Read the 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.

Being tested
niraparib, Physician's choice
Keywords
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, BRCA1 Gene Mutation, BRCA2 Gene Mutation, PARP Inhibitor, BRCA
Medical subject headings
Breast Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • niraparibDrug

    Also called formerly MK-4827

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

  • Physician's choiceDrug

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

Study groups in NCT01905592
Study groupRoleWhat they receive
Physician's choiceActive comparatorPhysician may select from 4 active comparators
Receives: Drug: Physician's choice
niraparibExperimentalPatients will be randomized 2:1 to receive niraparib 300 mg (3x100 mg capsules) once daily for 21 continuous days
Receives: Drug: niraparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. Overall Survival

    Overall Survival (OS) was defined as the time from randomization to the date of death of any causes.

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

  2. Number of Participants With Central BRCA Mutation Status

    Blood samples were collected to evaluate central BRCA mutation status of participants. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Number of participants with central BRCA mutation status as BRCA1 positive only, BRCA2 positive only, Rearrangement only, BRCA1 and BRCA2 positive, BRCA1 positive and rearrangement, and BRCA2 positive and rearrangement were reported.

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

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

    An adverse event (AE) 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 this treatment. An SAE is defined as any untoward medical occurrence or effect in a participant, whether or not considered related to the protocol treatment, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing participant hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an medically important event or reaction as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.

    Measured: Up to 7 years

  4. Progression Free Survival (PFS) - Investigator Assessment

    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 RECIST version 1.1 as determined by Investigator assessment. Progressive Disease is defined as at least a 20 % 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 mm.

    Measured: Assessed up to 4 years

  5. Time to Treatment Failure

    Time to treatment failure was defined from the date of randomization to progression or discontinuation of treatment for any reason, including but not restricted to disease progression, treatment toxicity and death.

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

  6. Overall Response Rate (ORR)

    ORR was defined as the percentage of the participants who achieved a complete response (CR) or partial response (PR) to treatment evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR)=disappearance of all target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. Partial Response (PR)= at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Percentage values are rounded off up to 1 decimal.

    Measured: Up to 4 years

  7. Duration of Response (DOR)

    Duration of response was defined as the time from first documentation of response (confirmed CR or PR) until the time of first documentation of disease progression by RECIST v1.1 or death by any cause.

    Measured: Up to 4 years

  8. Number of Participants With Serious Adverse Events Related to New Malignancy

    The number of participants with serious adverse events related to new malignancy were reported.

    Measured: Up to 7 years

  9. Number of Participants With Subsequent Anticancer Therapies

    The number of participants with subsequent anticancer therapies were evaluated. Data has been reported as per following categories: any new anitumoral therapy, any chemotherapy, any radiotherapy, any surgery, any hormonal therapy, any targeted agents, and any other treatment. Participants may have received more than one subsequent therapies.

    Measured: Up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2013 (estimated)
  2. Study start25 Feb 2014
  3. Primary completion23 May 2018
  4. Study completion26 Oct 2021

Why it stopped: The study was terminated due to futility.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations.
Masking
None (open label)
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01905592
Sponsor's protocol ID
213551
Other IDs
1307-BCG, BIG5-13, PR-30-5010-C
Acronym
BRAVO
Status last verified
Oct 2022
First submitted
18 Jul 2013
Last updated
15 Nov 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing niraparib and Physician's choice in people with Neoplasms, Breast and Carcinoma of Breast, run by Tesaro, Inc. at 104 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, United Kingdom, Italy, Spain, France and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) - Central Review Assessment (time frame: From the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier, up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01905592.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2022.

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