Trial record 1 of 2 for:
NCT01905592
A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients (BRAVO)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01905592 |
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Recruitment Status :
Terminated
(The study was terminated due to futility.)
First Posted : July 23, 2013
Results First Posted : August 27, 2020
Last Update Posted : November 15, 2022
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Sponsor:
Tesaro, Inc.
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Breast International Group
Myriad Genetic Laboratories, Inc.
US Oncology Research
Sarah Cannon
Facing Our Risk of Cancer Empowered
Information provided by (Responsible Party):
Tesaro, Inc.
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasms, Breast Carcinoma of Breast Human Epidermal Growth Factor 2 Negative Carcinoma of Breast BRCA1 Gene Mutation BRCA2 Gene Mutation Ovarian Neoplasms | Drug: niraparib Drug: Physician's choice | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 216 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 25, 2014 |
| Actual Primary Completion Date : | May 23, 2018 |
| Actual Study Completion Date : | October 26, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Physician's choice
Physician may select from 4 active comparators
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Drug: Physician's choice
Choice of 4 standard of care metastatic breast cancer chemotherapies, until progression or unacceptable toxicity develops |
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Experimental: niraparib
Patients will be randomized 2:1 to receive niraparib 300 mg (3x100 mg capsules) once daily for 21 continuous days
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Drug: niraparib
300 mg (3x100 mg capsules) once daily until progression or unacceptable toxicity develops
Other Name: formerly MK-4827 |
Primary Outcome Measures :
- 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 ]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).
Secondary Outcome Measures :
- Overall Survival [ Time Frame: From treatment randomization to date of death of any cause, up to 4 years ]Overall Survival (OS) was defined as the time from randomization to the date of death of any causes.
- Number of Participants With Central BRCA Mutation Status [ Time Frame: At Baseline (Cycle 1 Day1) (Cycle duration was 21 days) ]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.
- Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) [ Time Frame: Up to 7 years ]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.
- Progression Free Survival (PFS) - Investigator Assessment [ Time Frame: Assessed up to 4 years ]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.
- Time to Treatment Failure [ Time Frame: Date of randomization to discontinuation of treatment for any reason, up to 4 years ]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.
- Overall Response Rate (ORR) [ Time Frame: Up to 4 years ]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.
- Duration of Response (DOR) [ Time Frame: Up to 4 years ]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.
- Number of Participants With Serious Adverse Events Related to New Malignancy [ Time Frame: Up to 7 years ]The number of participants with serious adverse events related to new malignancy were reported.
- Number of Participants With Subsequent Anticancer Therapies [ Time Frame: Up to 7 years ]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.
Other Outcome Measures:
- 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) [ Time Frame: Up to 7 years ]The number of participants with MCID status in EORTC-QLQ-C30 was planned to be evaluated.The EORTC- QLQ-C30 includes 30-items with single and multi-item scales. These include five functional scales (physical functioning, role functioning cognitive functioning, emotional functioning and social functioning), three symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss and financial difficulties). Response options are 1 to 4. The average score can be transformed to 0 to 100, a high score for functional scales/ GHS/QoL represents better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represents significant symptomatology.
- Number of Participants With Euroqol 5 Dimension 5 Level (EQ-5D-5L) Dimension Scores by Visit [ Time Frame: Up to 7 years ]The number of participants with EQ-5D-5L scores by visit were planned to be evaluated. EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility,self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale(no problems, slight problems, moderate problems, severe problems and extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were to be converted to a single index score. Range for EQ-5D-5L index score is 0 (worst health) to 100 (best health), higher the score better the health status.
- Number of Participants With Any Subsequent Therapies Post Discontinuation of Study Treatment and Association With Potential Survival Related Outcomes [ Time Frame: Up to 7 years ]The number of participants with any subsequent therapies post-discontinuation of study treatment and association with potential survival related outcomes were planned to be evaluated.
- Number of Participants With Presence of Genetic and Non-genetic Biomarkers [ Time Frame: Up to 7 years ]Biomarkers include germline and tumor mutations including somatic BRCA1 and 2 mutations, reversion mutations, loss of heterozygosity as well as genome landscape and transcriptional or functional measures of homologous recombination (HR) deficiency were planned to be evaluated.
- Number of Participants With Germline BRCA1 and BRCA2 Mutation Status in Association With Survival Related Outcomes [ Time Frame: Up to 7 years ]Participants with germline BRCA1 and BRCA2 mutation status in association with survival related outcomes were planned to be evaluated.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
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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
Exclusion Criteria:
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01905592
Locations
Show 104 study locations
Sponsors and Collaborators
Tesaro, Inc.
European Organisation for Research and Treatment of Cancer - EORTC
Breast International Group
Myriad Genetic Laboratories, Inc.
US Oncology Research
Sarah Cannon
Facing Our Risk of Cancer Empowered
Investigators
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Study Documents (Full-Text)
Documents provided by Tesaro, Inc.:
Documents provided by Tesaro, Inc.:
Study Protocol [PDF] January 20, 2017
Statistical Analysis Plan [PDF] August 11, 2020
Additional Information:
| Responsible Party: | Tesaro, Inc. |
| ClinicalTrials.gov Identifier: | NCT01905592 |
| Other Study ID Numbers: |
213551 1307-BCG, BIG5-13 ( Other Identifier: EORTC, BIG ) PR-30-5010-C ( Other Identifier: Tesaro ) |
| First Posted: | July 23, 2013 Key Record Dates |
| Results First Posted: | August 27, 2020 |
| Last Update Posted: | November 15, 2022 |
| Last Verified: | October 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
Keywords provided by Tesaro, Inc.:
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Human Epidermal Growth Factor 2 Negative Carcinoma of Breast BRCA1 Gene Mutation BRCA2 Gene Mutation PARP Inhibitor BRCA |
Additional relevant MeSH terms:
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Carcinoma Neoplasms Ovarian Neoplasms Breast Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Endocrine Gland Neoplasms Neoplasms by Site Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female |
Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Breast Diseases Skin Diseases Niraparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |