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

Gastric Cancer Clinical Trial

Official title:

A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00486356
• Other study ID #: 0284-04-FB
• Secondary ID: P30CA036727
• Status: Completed
• Phase: Phase 1
• Start date: October 1, 2004
• Est. completion date: January 1, 2010

Study information

• Verified date: December 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: January 1, 2010
• Est. primary completion date: January 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Cholangiocarcinoma
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Gastric Cancer
• Liver Cancer
• Liver Neoplasms
• Stomach Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• capecitabine

• carboplatin

• epirubicin hydrochloride

Genetic:
• microarray analysis

• polymorphism analysis

Other:
• pharmacological study

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center, Eppley Cancer Center	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
University of Nebraska	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose of capecitabine	Establish a recommended Phase II dose of oral capecitabine given twice daily on days 2-5, 8-12, and 15-19 in combination with fixed IV doses of epirubicin and carboplatin given day 1 of each 28-day cycle	Every 28-days until first documented progression up to 63 months
Primary	Toxicities of combined chemotherapy regimen	Evaluate all toxicities associated with this combination chemotherapy regimen: 1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening	Every 28-days until first documented progression up to 63 months
Secondary	End-of-infusion levels of epirubicin hydrochloride/metabolites and incidence of correlation with epirubicin hydrochloride dosing and clinical toxicity	Correlation of end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dosing and clinical toxicity (1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening)	Each day of dosing up to 63 months
Secondary	Correlation of the pharmacokinetics (speed of appearance in the blood plasma and its concentration) of capecitabine with clinical toxicity	Measure the pharmacokinetics of capecitabine and correlate these parameters with clinical toxicity	Each day of dosing up to 63 months
Secondary	Incidence of Correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity	Assess possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity	Post-treatment up to 63 months
Secondary	Antitumor activity	Document any anti-tumor activity (MTT assay is a quantitative and sensitive detection of cell proliferation as it measures the growth rate of cells by virtue of a linear relationship between cell activity and absorbance.)	Prior to cycle 1, and then every two 28 day cycles up to 63 months