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

Phase 1
18 Years
Not Enrolling
Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer, Liver Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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



- 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.


- 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

- 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.

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)

- 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


- 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


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose of capecitabine

Outcome Time Frame:

Every 28-days until progression.

Safety Issue:


Principal Investigator

Jean L. Grem, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska


United States: Institutional Review Board

Study ID:




Start Date:

October 2004

Completion Date:

January 2010

Related Keywords:

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



UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680