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

December 28, 2023 updated by: University of Nebraska

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198-6805
        • University of Nebraska Medical Center, Eppley Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: carboplatin
Other Names:
  • Paraplatin
Genetic: polymorphism analysis
Other: pharmacological study
Drug: capecitabine
Other Names:
  • Xeloda
Drug: epirubicin hydrochloride
Other Names:
  • Ellence
Genetic: microarray analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended phase II dose of capecitabine
Time Frame: Every 28-days until first documented progression up to 63 months
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
Toxicities of combined chemotherapy regimen
Time Frame: Every 28-days until first documented progression up to 63 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
End-of-infusion levels of epirubicin hydrochloride/metabolites and incidence of correlation with epirubicin hydrochloride dosing and clinical toxicity
Time Frame: Each day of dosing up to 63 months
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
Correlation of the pharmacokinetics (speed of appearance in the blood plasma and its concentration) of capecitabine with clinical toxicity
Time Frame: Each day of dosing up to 63 months
Measure the pharmacokinetics of capecitabine and correlate these parameters with clinical toxicity
Each day of dosing up to 63 months
Incidence of Correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity
Time Frame: Post-treatment up to 63 months
Assess possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity
Post-treatment up to 63 months
Antitumor activity
Time Frame: Prior to cycle 1, and then every two 28 day cycles up to 63 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jean L Grem, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2004

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

June 13, 2007

First Submitted That Met QC Criteria

June 13, 2007

First Posted (Estimated)

June 14, 2007

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

December 28, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0284-04-FB
  • P30CA036727 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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