Docetaxel Combined With Ketoconazole in Treatment of Breast Cancer
Patients with locally advanced or metastatic breast cancer and with measurable primary breast tumor will be treated with 70mg docetaxel combined with ketoconazole. Serial tumor biopsies and plasma samples will be taken for gene expression and proteomics studies to identify biomarkers that may predict for treatment response.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Docetaxel Combined With Ketoconazole in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor|
- 1. Evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer. [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
- 2. Evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
- 1. To study tumor genomics and proteomics and serum proteomics in breast cancer in response to docetaxel/ketoconazole. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 2. To compare tumor genomics and proteomics and serum proteomics in breast cancer in response to docetaxel/ketoconazole to that induced by docetaxel alone in a prior study (HO B17/02). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 3. To correlate docetaxel pharmacokinetics with (1)Genetic polymorphisms of drug metabolizing enzymes(2)Drug toxicity & tumor response(3)Peripheral mononuclear cell gene expression profiles [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- (4) To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2005|
|Study Completion Date:||June 2012|
|Primary Completion Date:||April 2007 (Final data collection date for primary outcome measure)|
|Experimental: docetaxel and ketoconazole||
Drug: docetaxel and ketoconazole
Docetaxel will be obtained locally from the manufacturer. Storage conditions for unopened vials, reconstitution, and storage conditions for the reconstituted solution will follow the manufacturer's recommendations. Docetaxel solutions should be prepared and stored in glass, polypropylene or polyolefin containers. Non-PVC containing and polyethylene-lined administration sets should be used.
Ketoconazole is available commercially in 200 mg tablet. Ketoconazole is to be administered at a dose of 200mg BID orally for six doses, starting two days before docetaxel administration. The fifth dose should be administered on the day of and before administering docetaxel, while the sixth dose should be administered in the evening of the day of docetaxel administration.
We hypothesize that 70mg docetaxel co-administered with ketoconazole would result in similar clinical efficacy as conventional doses of docetaxel (75mg/m2 body surface area) in terms of clinical and pathological response rates in metastatic breast cancer. We further hypothesize that tumor genomic and proteomic changes and serum proteomic changes would correlate with tumor response. We are also looking to correlate drug pharmacokinetics with treatment toxicity, genotype of drug metabolizing enzymes and transporters, and peripheral mononuclear cell gene expression profiles. The primary objectives are to evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer, and to evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole.