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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|ClinicalTrials.gov Identifier: NCT01905592|
Recruitment Status : Active, not recruiting
First Posted : July 23, 2013
Results First Posted : August 27, 2020
Last Update Posted : November 16, 2020
|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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||215 participants|
|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)|
|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|
|Estimated Study Completion Date :||December 14, 2022|
Active Comparator: Physician's choice
Physician may select from 4 active comparators
Drug: Physician's choice
Choice of 4 standard of care metastatic breast cancer chemotherapies, until progression or unacceptable toxicity develops
Patients will be randomized 2:1 to receive niraparib 300 mg (3x100 mg capsules) once daily for 21 continuous days
300 mg (3x100 mg capsules) once daily until progression or unacceptable toxicity develops
Other Name: formerly MK-4827
- 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 patients with advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gBRCAmut 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 1.1 as determined by central review assessment.
- Overall Survival [ Time Frame: From treatment randomization to date of death of any cause, up to 4 years ]To compare overall survival of patients with advanced/metastatic HER2-negative gBRCAmut breast cancer who have a gBRCAmut when treated with niraparib as compared to those treated with physician's choice. Overall Survival (OS) is defined as the time from randomization to the date of death of any causes.
- Determine Concordance Between gBRCAmut Tests for the Purpose of Developing a Commercial Companion Diagnostic Test [ Time Frame: End of study ]To establish germline BRCA (gBRCA) mutation status of screened patients using a centrally provided, validated test as well as future tests, and determine concordance between tests for the purpose of developing a commercial companion diagnostic test. The concordance of the candidate companion diagnostic test with the centralized gBRCA mutation test with respect to identifying gBRCA mutated patients will be evaluated using a separate blood sample. The sensitivity and specificity of the companion diagnostic test to the centralized validated test with respect to gBRCA status will be determined along with the corresponding 95% confidence intervals.
- Safety and Tolerability [ Time Frame: End of Study ]To evaluate safety and tolerability as measured by all adverse events (AEs). Safety and tolerability will be described using frequency of AEs and AEs of Common Terminology Criteria for Adverse Events (CTCAE) grade >=3. Safety analyses will include all patients who have received at least one dose of study drug and will be evaluated descriptively.
- 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.
- Time to Treatment Failure [ Time Frame: Date of randomization to discontinuation of treatment for any reason, up to 4 years ]To evaluate time to treatment failure (discontinuation of treatment for any reason). Time to treatment failure is 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. If progressive disease occurred earlier than treatment discontinuation, the date of progressive disease was considered the date of treatment failure. At the time of analysis, patients who were continuing to receive treatment were censored on the date of last contact.
- Response Rate and Duration of Response [ Time Frame: End of Study ]To compare response rate and duration of response. The best response (complete response [CR], partial response [PR], stable disease [SD] or disease progression [PD]) for each patient will be summarized by treatment arm. The overall response rate (ORR) (ORR = CR+PR) will be summarized by treatment arm along with the corresponding exact 2-sided 95% confidence interval. A chi-square test will be used to compare ORR between the treatment arms. Duration of response will be summarized for the subgroup of patients that obtained objective response (CR or PR) using the Kaplan-Meier method and be displayed graphically where appropriate. The median duration and 2-sided 95% confidence interval for the median will be provided for each treatment arm.
- To Compare Time to Deterioration of Health-related Quality of Life: QLQ-C30 and EQ-5D-5L [ Time Frame: 13 months ]To compare time to deterioration of health-related quality of life (HRQoL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EuroQol 5 Dimension 5 Level (EQ-5D-5L). Patient reported outcomes were collected via questionnaires (EORTC QLQ-C30 and EQ-5D-5L). These had to be completed within 4 weeks prior to randomization and subsequent questionnaires were filled in every 2 cycles (ie. 6 weeks) while on-treatment and every 3 months while in follow- up. Collection of HRQoL data was limited to the first 12 months after randomization. The primary HRQoL endpoint considered relevant for this study is time to HRQoL deterioration (TTQ). TTQ is defined as the time from randomization to death, progression or clinical relevant deterioration in pre-specified QLQ-C30 scales. Patients who had not experienced an event at the time of analysis were censored at the time of the last completed HRQoL assessment.
- Subsequent Therapies and Potential Relationships With Outcomes [ Time Frame: End of Study ]To describe subsequent therapies and potential relationships with outcomes
- Assess Genetic and Non-genetic Biomarkers [ Time Frame: End of Study ]To assess genetic and non-genetic biomarkers relating to treatment efficacy. Germline and tumor mutations may be explored 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.
- Assess Outcomes by Germline Mutation BRCA1 vs BRCA2 [ Time Frame: End of Study ]To assess outcomes by germline mutation BRCA1 vs BRCA2
- Post-treatment Data [ Time Frame: End of Study ]Descriptive summary statistics will be used to summarize post- treatment data (.i.e subsequent anticancer therapies and any new malignancy)
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
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|