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Sponsored by: |
Cancer Research UK |
---|---|
Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00664781 |
RATIONALE: AG014699 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 AG014699 and to see how well it works in treating patients with locally advanced or metastatic breast cancer or advanced ovarian cancer.
Condition | Intervention | Phase |
---|---|---|
brca1 Mutation Carrier brca2 Mutation Carrier Breast Cancer Ovarian Cancer |
Drug: PARP-1 inhibitor AG014699 Procedure: immunohistochemistry staining method Procedure: liquid chromatography Procedure: mass spectrometry Procedure: pharmacological study Procedure: protein expression analysis Procedure: western blotting |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Open Label |
Official Title: | A Cancer Research UK Phase II Proof of Principle Trial of the Activity of the Intravenous 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 |
Estimated Enrollment: | 68 |
Study Start Date: | December 2007 |
Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
Secondary
Tertiary
OUTLINE: This is a dose-escalation study followed by an open label multicenter study. Patients are stratified according to tumor type (breast vs ovarian) and mutation status ( BRCA 1 vs BRCA 2).
Patients receive PARP-1 inhibitor AG014699 IV (at one of several possible dosages) over 30 minutes once daily on days 1-5. 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 or CA 15.3) measurements, AG-014699 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Must meet 1 of the following criteria:
No more than 3 prior chemotherapy regimens for patients with breast or ovarian cancer
Measurable disease, as defined by RECIST criteria and measured by x-ray, CT scan, or MRI
PATIENT CHARACTERISTICS:
No other concurrent malignancy, except adequately treated cone-biopsied carcinoma in situ of the uterine cervix, basal cell or squamous cell carcinoma of the skin, or breast and ovarian carcinoma
No active or unstable cardiac disease or history of myocardial infarction within the past 6 months
PRIOR CONCURRENT THERAPY:
United Kingdom, England | |
Cancer Research UK and University College London Cancer Trials Centre | Recruiting |
London, England, United Kingdom, W1T 4TJ | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Christie Hospital | Recruiting |
Manchester, England, United Kingdom, M20 4BX | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Derriford Hospital | Recruiting |
Plymouth, England, United Kingdom, PL6 8DH | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Leeds Cancer Centre at St. James's University Hospital | Recruiting |
Leeds, England, United Kingdom, LS9 7TF | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Northern Centre for Cancer Treatment at Newcastle General Hospital | Recruiting |
Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust | Recruiting |
Birmingham, England, United Kingdom, B15 2TT | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Southampton General Hospital | Recruiting |
Southampton, England, United Kingdom, SO16 6YD | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
United Kingdom, Scotland | |
Beatson West of Scotland Cancer Centre | Recruiting |
Glasgow, Scotland, United Kingdom, G12 0YN | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk | |
Edinburgh Cancer Centre at Western General Hospital | Recruiting |
Edinburgh, Scotland, United Kingdom, EH4 2XU | |
Contact: Contact Person 44-191-256-3599 ruth.plummer@newcastle.ac.uk |
Principal Investigator: | Ruth Plummer | Northern Centre for Cancer Treatment at Newcastle General Hospital |
Study ID Numbers: | CDR0000593558, CRUK-PH2/052, CRUK-PARP/BRCA, EU-20842, EUDRACT-2006-002348-27 |
Study First Received: | April 22, 2008 |
Last Updated: | September 22, 2008 |
ClinicalTrials.gov Identifier: | NCT00664781 |
Health Authority: | Unspecified |
stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer recurrent breast cancer stage III ovarian epithelial cancer stage IV ovarian epithelial cancer |
recurrent ovarian germ cell tumor stage III ovarian germ cell tumor stage IV ovarian germ cell tumor ovarian stromal cancer ovarian sarcoma BRCA1 mutation carrier BRCA2 mutation carrier |
Ovarian cancer Ovarian Neoplasms Skin Diseases Gonadal Disorders Malignant mesenchymal tumor Genital Neoplasms, Female Breast Neoplasms Endocrine System Diseases Urogenital Neoplasms |
Ovarian Diseases Ovarian epithelial cancer Soft tissue sarcomas Recurrence Genital Diseases, Female Sarcoma Endocrinopathy Breast Diseases Endocrine Gland Neoplasms |
Neoplasms Neoplasms by Site Adnexal Diseases |