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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00486356
First received: June 13, 2007
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Gastric Cancer
Liver Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: capecitabine
Drug: carboplatin
Drug: epirubicin hydrochloride
Genetic: microarray analysis
Genetic: polymorphism analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Recommended phase II dose of capecitabine [ Time Frame: Every 28-days until progression. ] [ Designated as safety issue: Yes ]
  • Toxicities [ Time Frame: Every 28-days until progression. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Correlation of end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dosing and clinical toxicity [ Time Frame: Each day of dosing ] [ Designated as safety issue: Yes ]
  • Correlation of the pharmacokinetics of capecitabine with clinical toxicity [ Time Frame: Each day of dosing ] [ Designated as safety issue: Yes ]
  • Possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity [ Time Frame: Post-treatment ] [ Designated as safety issue: Yes ]
  • Antitumor activity [ Time Frame: Prior to cycle 1 and then every 2 cycles ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: October 2004
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Capecitabine, Epirubicin, and Carboplatin Drug: capecitabine Drug: carboplatin Drug: epirubicin hydrochloride Genetic: microarray analysis Genetic: polymorphism analysis Other: pharmacological study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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)
  • No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy)
  • No leukemia or lymphoma
  • No primary CNS malignancies or CNS metastases

PATIENT CHARACTERISTICS:

  • 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)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 1.6 mg/dL
  • Left ventricular ejection fraction ≥ 50%
  • 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
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior doxorubicin at cumulative doses > 300 mg/m²
  • 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
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent cimetidine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486356

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Jean L. Grem, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT00486356     History of Changes
Other Study ID Numbers: 284-04, P30CA036727, UNMC-28404
Study First Received: June 13, 2007
Last Updated: May 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
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

Additional relevant MeSH terms:
Bile Duct Neoplasms
Gallbladder Neoplasms
Liver Neoplasms
Stomach Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Biliary Tract Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gallbladder Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Site
Stomach Diseases
Capecitabine
Carboplatin
Epirubicin
Fluorouracil
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014