NCT00664781

Rucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer

A Cancer Research UK Phase II Proof of Principle Trial of the Activity of the PARP-1 Inhibitor, AG-014699, in Known Carriers of a BRCA 1 or BRCA 2 Mutation With Locally Advanced or Metastatic Breast or Advanced Ovarian Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• brca1 Mutation Carrier
• brca2 Mutation Carrier
• Breast Cancer
• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	rucaparib (CO-338; formally AG-014699 or PF-01367338)
GENETIC	protein expression analysis
GENETIC	western blotting
OTHER	immunohistochemistry staining method
OTHER	liquid chromatography
OTHER	mass spectrometry
OTHER	pharmacological study

Timeline

• Start date: 2007-12-01
• Primary completion: 2015-01-01
• Completion: 2015-01-01
• First posted: 2008-04-23
• Last updated: 2016-05-24

Locations

7 sites across 1 country: United Kingdom