Rucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer
- Conditions
- Ovarian CancerBreast Cancerbrca1 Mutation Carrierbrca2 Mutation Carrier
- Registration Number
- NCT00664781
- Lead Sponsor
- Cancer Research UK
- Brief Summary
RATIONALE: rucaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying the side effects and best dose of rucaparib and to see how well it works in treating patients with locally advanced or metastatic breast cancer or advanced ovarian cancer.
- Detailed Description
OBJECTIVES:
Primary
* Assessment of Anti tumour activity to PARP-1 inhibitor rucaparib in patients with locally advanced or metastatic breast or advanced ovarian cancer shown to express the BRCA 1 or 2 mutations.
* To evaluate the toxicity of treatment with Rucaparib in these population's.
Secondary
* To evaluate the time to progression and overall survival in patients treated with this drug.
* To study pharmacokinetics of this drug in these patient populations.
* To evaluate the Poly(ADP-ribose) polymerase (PARP) activity in peripheral blood lymphocytes from BRCA 1 and 2 heterozygotic patients.
* To determine a tolerable and effective dosing regimen of the Rucaparib oral formulation.
OUTLINE: This is a dose-escalation study followed by an open label multicenter study. The study was originally set up with an IV formulation. An oral formulation of the PARP-1 inhibitor rucaparib will be used from now on. Patients are stratified according to tumor type (breast vs ovarian) and mutation status ( BRCA 1 vs BRCA 2). In addition, patient with high-grade serous ovarian cancer can be enrolled into Stage 1 of the study. All patients enrolled will receive PARP-1 inhibitor rucaparib oral formulation once daily for either 7, 14, or 21 days of each cycle, (two possible dosages for 21 days treatment). Treatment repeats every 21 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable or responding disease may receive additional courses of treatment at the discretion of the chief investigator or Drug Development Office (DDO).
Patients undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for tumor marker (CA 125 and/or CA 15.3) measurements, rucaparib plasma levels via liquid chromatography/mass spectrometry/mass spectrometry, PARP activity, and PARP protein expression via western blotting immunoassays. Paraffin embedded sections from original diagnostic biopsy are also collected and analyzed for PARP protein expression via immunohistochemical technique. Pleural and ascitic fluid may be collected and analyzed for DNA DS break repair proficiency via immunohistochemical technique. Some patients also undergo biopsy of tumors and samples are analyzed for BRCA 2 mutation as well as PARP activity via validated PARP immunoblotting assay.
After completion of study treatment, patients are followed for 28 days.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 78
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Assessment of antitumor activity according to RECIST using tumor size measured clinically or radiologically with CT scan, MRI, plain x-ray, or other imaging techniques Safety profile
- Secondary Outcome Measures
Name Time Method Time to progression and overall survival Plasma levels measured by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry Poly(ADP-ribose) polymerase (PARP) activity measured ex vivo using validated assays To determine the optimal oral dosing regimen, based on the assessment of antitumor activity and the safety profile
Trial Locations
- Locations (7)
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
🇬🇧Birmingham, England, United Kingdom
Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care, Level 2, Freeman Hospital
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Cancer Research UK and University College London Cancer Trials Centre
🇬🇧London, England, United Kingdom
Christie Hospital
🇬🇧Manchester, England, United Kingdom
Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom