RUBY: A Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: rucaparib
600 mg bid per os , 28 day cycle, number of cycles: until progression or unacceptable toxicity develops.
|
Outcome Measures
Primary Outcome Measures
- Clinical Benefit Rate [3 years]
according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks
Secondary Outcome Measures
- Number of patients with complete response, partial response or stable disease [3 years]
complete response , partial response, or stable disease according to RECIST
- Progression free survival [3 years]
Progression free survival will be assessed from the time of the first dose to disease progression or death from any cause, whichever comes first.
- Overall Survival [3 years]
Overall survival will be assessed from the time of the first dose to death from any cause
- 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]
Adverse events are graded according to the CTCAE V4.03
Eligibility Criteria
Criteria
Inclusion Criteria:
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Women with histologically proven breast cancer.
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No Her2 over-expression.
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Progressive metastatic disease previously treated with at least one line of chemotherapy at the metastatic setting.
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Molecular analysis using the Affymetrix (CytoScan HD, SNP 6.0, or OncoScan) array available from the SAFIR02 protocol, or from other programs.
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BRCAness profile as defined by the Clovis genomic signature or BRCA1/2 somatic mutation (without known germline BRCA).
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Age ≥ 18 years
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WHO Performance Status 0/1
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Presence of measurable target lesion according to RECIST criteria v1.1
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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.
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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.
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Women of childbearing potential must have a negative serum pregnancy test done within 14 days of enrollment and/or urine pregnancy test 72 hours prior to the administration of the study drug.
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Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose.
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Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
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Patient with social insurance coverage.
Exclusion Criteria:
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BRCA1 or 2 germline known mutation.
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Life expectancy <3 months.
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Less than 14 days from radiotherapy (whatever the indication). Fields should not have involved all target lesions.
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Patients previously treated with a PARP inhibitor.
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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).
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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
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Inability to swallow
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Major problem with intestinal absorption
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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.
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Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
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Previous history of myelodysplastic syndrome
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History of hypersensitivity to active or inactive excipients of the rucaparib.
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Toxicities of grade ≥2 from any previous anti-cancer therapy, with the exception of alopecia.
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Altered haematopoietic or organ function, as indicated by the following criteria:
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Polynuclear neutrophils <1.5 x 10⁹/L
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Platelets <100 x 10⁹/L
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Haemoglobin <90 g/L
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ALAT/ASAT >2.5 x upper limit of normal (ULN) in the absence of or >5 x ULN in the presence of liver metastases
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Bilirubin >1.5 x ULN
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Creatinine clearance ≤30 mL/min (measured or calculated by Cockcroft and Gault formula
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Women who are pregnant.
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Patients using drugs that are known potent inhibitors or potent inducers of CYP1A2 or CYP3A4 are not eligible if those treatments cannot be substituted before inclusion
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Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
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Individuals deprived of liberty or placed under the authority of a tutor.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Leon Berard | Lyon | France | ||
| 2 | Institut Paoli Calmettes | Marseille | France |
Sponsors and Collaborators
- UNICANCER
- Clovis Oncology, Inc.
- Fondation ARC
Investigators
- Principal Investigator: Fabrice André, MD PhD, Gustave Roussy Villejuif
- Principal Investigator: Anne Patsouris, MD, Institut de Cancerologie de l'Ouest Paul Papin
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UC-0105/1501