Capecitabine, Epirubicin, and Carboplatin in Treating Patients With Progressive, Unresectable, or Metastatic Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine, epirubicin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
Primary
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Determine the recommended phase II dose of capecitabine when given together with epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or metastatic cancer.
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Determine the toxicities of this regimen in these patients.
Secondary
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Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dose and clinical toxicity in these patients.
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Correlate the pharmacokinetics of capecitabine with clinical toxicity in these patients.
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Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity in these patients.
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Document antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive epirubicin hydrochloride IV over 2 hours and carboplatin IV over 30 minutes on day 1 and oral capecitabine twice daily on days 2-5, 8-12, and 15-19. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Peripheral blood is collected for pharmacokinetic and pharmacogenetic studies before beginning study treatment and periodically during study. Samples for the pharmacogenetic studies are analyzed for correlation between polymorphisms in the promoter region of the thymidylate synthase gene and clinical toxicity. Patients also undergo bone marrow aspirate before beginning study treatment for molecular profiling studies.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Capecitabine, Epirubicin, and Carboplatin
|
Drug: capecitabine
Drug: carboplatin
Drug: epirubicin hydrochloride
Genetic: microarray analysis
Genetic: polymorphism analysis
Other: pharmacological study
|
Outcome Measures
Primary Outcome Measures
- Recommended phase II dose of capecitabine [Every 28-days until progression.]
- Toxicities [Every 28-days until progression.]
Secondary Outcome Measures
- Correlation of end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dosing and clinical toxicity [Each day of dosing]
- Correlation of the pharmacokinetics of capecitabine with clinical toxicity [Each day of dosing]
- Possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity [Post-treatment]
- Antitumor activity [Prior to cycle 1 and then every 2 cycles]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Pathologically confirmed cancer, meeting 1 of the following criteria:
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Disease that has progressed on standard therapy
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Locally advanced but unresectable primary or recurrent solid tumor
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Metastatic disease, including previously untreated metastatic disease for which study regimen represents reasonable initial chemotherapy with palliative intent (e.g., metastatic gastric cancer, hepatobiliary cancer, or cancer for which no effective standard therapy exists)
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No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy)
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No leukemia or lymphoma
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No primary CNS malignancies or CNS metastases
PATIENT CHARACTERISTICS:
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ECOG performance status 0-2
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Absolute neutrophil count ≥ 2,000/mm³
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Platelet count ≥ 100,000/mm³
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Bilirubin ≤ 1.5 times upper limit of normal (ULN)
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AST and ALT ≤ 2.5 times ULN
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Creatinine ≤ 1.6 mg/dL
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Left ventricular ejection fraction ≥ 50%
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No other medical illness that would preclude study treatment
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No active infection requiring IV antibiotic therapy unless the infection has resolved
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No history of allergy to platinum compounds, mannitol, or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
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No history of unexpectedly severe intolerance to fluorouracil
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
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See Disease Characteristics
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Recovered from prior therapy
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No prior doxorubicin at cumulative doses > 300 mg/m²
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More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) or immunotherapy
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At least 2 weeks since prior radiotherapy
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At least 8 weeks since prior strontium therapy
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At least 4 weeks since prior and no concurrent sorivudine or brivudine
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No concurrent combination antiretroviral therapy for HIV-positive patients
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No concurrent cimetidine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-6805 |
Sponsors and Collaborators
- University of Nebraska
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jean L. Grem, MD, University of Nebraska
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 284-04
- P30CA036727
- UNMC-28404