Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Metastatic Breast Cancer
Trial Information
Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors
This is a phase I study using an accelerated titration design to determine the maximum
tolerated dose (MTD) of capecitabine given orally on a BID schedule from days 1-14, in
combination with docetaxel given at a fixed dose of 75 mg/m2 IV on day 8. Once the MTD of
capecitabine has been determined, an additional nine patients with accessible tumors will be
treated at the MTD. Pharmacokinetics of plasma capecitabine, 5-FU,
5'-deoxy-5-fluorouridine, and docetaxel will be assayed in these nine patients, and tumor
biopsies will be taken to assess Bax:Bcl-2 ratios and Bcl-2 phosphorylation at several time
points. The primary aim of this study will be to determine the maximum tolerated dose and
dose limiting toxicities of capecitabine when given with a fixed dose of docetaxel on day 8
of a 21 day schedule. Secondary aims will include assessment of the pharmacokinetics of
capecitabine and docetaxel on this schedule, and determination of intratumoral Bax:Bcl-2,
Bcl-2 phosphorylation, and DPD expression, and correlation with clinical toxicities and
antitumor response.
Inclusion Criteria:
- Patients with a histologically or cytologically proven metastatic solid tumor.
- Patients with measurable disease or an evaluable bone lesion that will not undergo
biopsy.
- Patients treated within the additional cohort at MTD will have metastatic breast
cancer with a site of disease that is amenable to percutaneous FNA and must be
willing to undergo serial FNA biopsies of their primary tumor.
- Age > 18 years.
- Life expectancy of at least 6 months.
- ECOG performance status 0-2.
- Adequate hematologic, hepatic, and renal function
- Patients must have an intact upper gastrointestinal tract, be able to swallow
tablets, and not have a malabsorption syndrome.
Exclusion Criteria:
- No significant uncontrolled infectious or cardiovascular disease, or a myocardial
infarction within the prior 12 months.
- No prior organ allograft.
- No prior treatment with capecitabine or with docetaxel.
- No prior unanticipated severe reaction to fluoropyrimidine therapy or known
hypersensitivity to 5-fluorouracil.
- No concurrent antacid therapy is allowed.
- No other significant medical/surgical diseases.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the maximum tolerated dose, and dose limiting toxicity of capecitabine when given daily for 14 days with docetaxel given on day 8 of a 21 day cycle
Outcome Time Frame:
3 weeks
Safety Issue:
Yes
Principal Investigator
Gary N Schwartz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Norris Cotton Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
D-0139
NCT ID:
NCT00169000
Start Date:
January 2003
Completion Date:
March 2006
Related Keywords:
- Metastatic Breast Cancer
- breast cancer
- capecitabine
- docetaxel
- pharmacokinetic/pharmacodynamic
- bcl-2
- bax
- Breast Neoplasms
Name | Location |
|---|---|
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
