Capecitabine, Epirubicin, and Carboplatin in Treating Patients With Progressive, Unresectable, or Metastatic Cancer

NCT ID: NCT00486356

Last Updated: 2024-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-01
• Study Completion Date: 2010-01-01

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.

Detailed Description

OBJECTIVES:

Primary

• Determine the recommended phase II dose of capecitabine when given together with epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or metastatic cancer.
• Determine the toxicities of this regimen in these patients.

Secondary

• Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dose and clinical toxicity in these patients.
• Correlate the pharmacokinetics of capecitabine with clinical toxicity in these patients.
• Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity in these patients.
• 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.

Conditions

Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Capecitabine, Epirubicin, and Carboplatin

Determine the recommended phase II dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer.

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

carboplatin

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

microarray analysis

Intervention Type: GENETIC

polymorphism analysis

Intervention Type: GENETIC

pharmacological study

Intervention Type: OTHER

Interventions

capecitabine

Intervention Type: DRUG

carboplatin

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

microarray analysis

Intervention Type: GENETIC

polymorphism analysis

Intervention Type: GENETIC

pharmacological study

Intervention Type: OTHER

Other Intervention Names

Xeloda; Paraplatin; Ellence

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed cancer, meeting 1 of the following criteria:

• Disease that has progressed on standard therapy
• Locally advanced but unresectable primary or recurrent solid tumor
• 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)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• alanine aminotransferase (ALT) & aspartate aminotransferase (AST) ≤ 2.5 times ULN
• Creatinine ≤ 1.6 mg/dL
• Left ventricular ejection fraction ≥ 50%
• Fertile patients must use effective contraception
• Recovered from prior therapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) or immunotherapy
• At least 2 weeks since prior radiotherapy
• At least 8 weeks since prior strontium therapy
• At least 4 weeks since prior and no concurrent sorivudine or brivudine

Exclusion Criteria

• No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy)
• No leukemia or lymphoma
• No primary central nervous system (CNS) malignancies or CNS metastases
• No other medical illness that would preclude study treatment
• No active infection requiring IV antibiotic therapy unless the infection has resolved
• No history of allergy to platinum compounds, mannitol, or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
• No history of unexpectedly severe intolerance to fluorouracil
• Not pregnant or nursing/negative pregnancy test
• No prior doxorubicin at cumulative doses > 300 mg/m²
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent cimetidine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean L Grem, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center, Eppley Cancer Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0284-04-FB

Identifier Type: -

Identifier Source: org_study_id