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A Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature

NCT02505048

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature
  • Official Title: A Single Arm, Open-label, Phase II Study to Assess the Efficacy of Rucaparib in Metastatic Breast Cancer Patients With a BRCAness Genomic Signature

Clinical Trial IDs

  • ORG STUDY ID: UC-0105/1501
  • NCT ID: NCT02505048

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
rucaparibrucaparib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
rucaparibExperimentalTablets 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
  • rucaparib

Eligibility Criteria

        Inclusion Criteria:

          1. Women with histologically proven breast cancer.

          2. No Her2 over-expression.

          3. Progressive metastatic disease previously treated with at least one line of
             chemotherapy at the metastatic setting.

          4. Molecular analysis using the Affymetrix (CytoScan HD, SNP 6.0, or OncoScan) array
             available from the SAFIR02 protocol, or from other programs.

          5. BRCAness profile as defined by the Clovis genomic signature or BRCA1/2 somatic
             mutation (without known germline BRCA).

          6. Age ≥ 18 years

          7. WHO Performance Status 0/1

          8. Presence of measurable target lesion according to RECIST criteria v1.1

          9. 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.

         10. 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.

         11. 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.

         12. Women who are breastfeeding should discontinue nursing prior to the first dose of
             study drug and until 6 months after the last dose.

         13. Provision of signed and dated, written informed consent prior to any study specific
             procedures, sampling and analyses

         14. Patient with social insurance coverage.

        Exclusion Criteria:

          1. BRCA1 or 2 germline known mutation.

          2. Life expectancy < 3 months.

          3. Less than 14 days from radiotherapy (whatever the indication). Fields should not have
             involved all target lesions.

          4. Patients previously treated with a PARP inhibitor.

          5. 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).

          6. 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

          7. Inability to swallow

          8. Major problem with intestinal absorption

          9. 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.

         10. Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or
             active Hepatitis B, C and HIV)

         11. Previous history of myelodysplastic syndrome

         12. History of hypersensitivity to active or inactive excipients of the rucaparib.

         13. Toxicities of grade ≥2 from any previous anti-cancer therapy, with the exception of
             alopecia.

         14. Altered haematopoietic or organ function, as indicated by the following criteria:

               -  Polynuclear neutrophils < 1.5 x 109/L

               -  Platelets < 100 x 109/L

               -  Haemoglobin < 90 g/L

               -  ALAT/ASAT > 2.5x ULN in the absence of or > 5x ULN in the presence of liver
                  metastases

               -  Bilirubin > 1.5xULN

               -  Creatinine clearance ≤30 mL/min (measured or calculated by Cockroft and Gault
                  formula

         15. Women who are pregnant.

         16. 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

         17. 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.

         18. Individuals deprived of liberty or placed under the authority of a tutor.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit Rate
Time Frame:3 years
Safety Issue:
Description:according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks

Secondary Outcome Measures

Measure:Number of patients with complete response, partial response or stable disease
Time Frame:3 years
Safety Issue:
Description:complete response , partial response, or stable disease according to RECIST
Measure:Progression free survival
Time Frame:3 years
Safety Issue:
Description:Progression free survival will be assessed from the time of the first dose to disease progression or death from any cause, whichever comes first.
Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:Overall survival will be assessed from the time of the first dose to death from any cause
Measure:Number of patients experiencing an adverse event.
Time Frame:toxicities will be assessed during the whole treatment period (6 months expected in average) followed by a 2-year post-treatment follow-up period
Safety Issue:
Description:Adverse events are graded according to the CTCAE V4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNICANCER

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