Capecitabine, Epirubicin, and Carboplatin in Treating Patients With Progressive, Unresectable, or Metastatic Cancer
Condition: Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Stomach Neoplasms; Liver Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): capecitabine; carboplatin; epirubicin hydrochloride; microarray analysis; polymorphism analysis; pharmacological study
Intervention type(s): Drug; Drug; Drug; Genetic; Genetic; Other
Other intervention name(s): Xeloda; Paraplatin; Ellence
Intervention MeSH terms: Carboplatin; Capecitabine; Epirubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified adult solid tumor, protocol specific; recurrent gastric cancer; stage IV gastric cancer; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; recurrent extrahepatic bile duct cancer; unresectable extrahepatic bile duct cancer; recurrent gallbladder cancer; unresectable gallbladder cancer