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

Metastatic Breast Cancer Clinical Trial

— RUBY  

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 Details — Status: Completed

Administrative data

• NCT number: NCT02505048
• Other study ID #: UC-0105/1501
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: December 2019

Study information

• Verified date: June 2021
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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 10?/L
• Platelets <100 x 10?/L
• Haemoglobin <90 g/L
• ALAT/ASAT >2.5 x upper limit of normal (ULN) in the absence of or >5 x ULN in the presence of liver metastases
• Bilirubin >1.5 x ULN
• Creatinine clearance =30 mL/min (measured or calculated by Cockcroft 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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• rucaparib
600 mg bid per os , 28 day cycle, number of cycles: until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon
France	Institut Paoli Calmettes	Marseille

Sponsors (3)

Lead Sponsor	Collaborator
UNICANCER	Clovis Oncology, Inc., Fondation ARC

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Benefit Rate	according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks	3 years
Secondary	Number of patients with complete response, partial response or stable disease	complete response , partial response, or stable disease according to RECIST	3 years
Secondary	Progression free survival	Progression free survival will be assessed from the time of the first dose to disease progression or death from any cause, whichever comes first.	3 years
Secondary	Overall Survival	Overall survival will be assessed from the time of the first dose to death from any cause	3 years
Secondary	Number of patients experiencing an adverse event.	Adverse events are graded according to the CTCAE V4.03	toxicities will be assessed during the whole treatment period (6 months expected in average) followed by a 2-year post-treatment follow-up period