A Single Arm, Open-label, Phase II Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature
Overview
- Phase
- Phase 2
- Intervention
- rucaparib
- Conditions
- Metastatic Breast Cancer
- Sponsor
- UNICANCER
- Enrollment
- 41
- Locations
- 2
- Primary Endpoint
- Clinical Benefit Rate
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to assess the efficacy of a PARP inhibitor, rucaparib, in progressing breast cancer patients and who are carrying a BCRAness profile defined by genomic signature or BRCA 1 or 2 somatic mutation, without known BRCA 1 or 2 germline mutation.
Detailed Description
This is a single arm, open-label, multicentric, phase II trial, with a Simon two-stage design, assessing the efficacy of a PARP inhibitor, rucaparib, in 41 progressing breast cancer patients with at least one line of chemotherapy at the metastatic setting., and who are carrying a BRCAness profile defined by Clovis genomic signature or a BRCA1 or 2 somatic mutation, without known BRCA1 or 2 germline mutation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Women with histologically proven breast cancer.
- •No Her2 over-expression.
- •Progressive metastatic disease previously treated with at least one line of chemotherapy at the metastatic setting.
- •Molecular analysis using the Affymetrix (CytoScan HD, SNP 6.0, or OncoScan) array available from the SAFIR02 protocol, or from other programs.
- •BRCAness profile as defined by the Clovis genomic signature or BRCA1/2 somatic mutation (without known germline BRCA).
- •Age ≥ 18 years
- •WHO Performance Status 0/1
- •Presence of measurable target lesion according to RECIST criteria v1.1
- •Patients will have had at least a 21-day wash-out period from last chemotherapy or targeted therapy administration prior to inclusion and should have recover (grade ≤1) from all residual toxicities, excluding alopecia.
- •Potentially reproductive patients must agree to use an effective contraceptive non-hormonal method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 6 months after the last dose of study drug.
Exclusion Criteria
- •BRCA1 or 2 germline known mutation.
- •Life expectancy \<3 months.
- •Less than 14 days from radiotherapy (whatever the indication). Fields should not have involved all target lesions.
- •Patients previously treated with a PARP inhibitor.
- •Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug).
- •Patients with all target lesions in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
- •Inability to swallow
- •Major problem with intestinal absorption
- •Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
- •Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
Arms & Interventions
rucaparib
Tablets 200 mg and 300 mg per os : 600 mg / bid every day in continuous. Patients will be treated with rucaparib Cycles are defined in 28-day periods Disease response will be assessed every 8 weeks (RECIST 1.1) Safety will be assessed continuously
Intervention: rucaparib
Outcomes
Primary Outcomes
Clinical Benefit Rate
Time Frame: 3 years
according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks
Secondary Outcomes
- Number of patients with complete response, partial response or stable disease(3 years)
- Progression free survival(3 years)
- Overall Survival(3 years)
- Number of patients experiencing an adverse event.(toxicities will be assessed during the whole treatment period (6 months expected in average) followed by a 2-year post-treatment follow-up period)