Epirubicin, Carboplatin, and Capecitabine in Treating Patients With Unresectable Locally Advanced, Metastatic, or Recurrent Solid Tumor
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining epirubicin, carboplatin, and capecitabine in treating patients who have unresectable locally advanced, metastatic, or recurrent solid tumor.
| Condition | Intervention | Phase |
|---|---|---|
|
Esophageal Cancer Extrahepatic Bile Duct Cancer Gastric Cancer Head and Neck Cancer Liver Cancer Unspecified Adult Solid Tumor, Protocol Specific |
Drug: capecitabine Drug: carboplatin Drug: epirubicin hydrochloride |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | A Phase I/II Trial of Epirubicin, Carboplatin & Capecitabine in Adult Cancer Patients |
| Study Start Date: | July 2001 |
| Study Completion Date: | June 2004 |
OBJECTIVES:
- Determine the maximum tolerated dose and the recommended phase II dose of capecitabine administered with epirubicin and carboplatin in patients with unresectable locally advanced, metastatic, or recurrent solid tumors.
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics (PK) of capecitabine and correlate these PK parameters with clinical toxicity of this regimen in these patients.
- Correlate end-of-infusion levels of epirubicin and its metabolites with epirubicin dose and clinical toxicity of this regimen in these patients.
- Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity of this regimen in these patients.
- Determine the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive epirubicin 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. Courses repeat every 4 weeks 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. Once the MTD is determined, 24 additional patients are treated at the recommended phase II dose.
PROJECTED ACCRUAL: A total of 3-45 patients (24 patients for phase II) will be accrued for this study within 2 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed solid tumor
Progressive disease on standard therapy, including:
- Locally advanced, unresectable primary or recurrent tumor OR
- Metastatic disease
- Previously untreated metastatic cancer for which study regimen represents reasonable initial chemotherapy with palliative intent (e.g., metastatic gastric cancer, hepatobiliary cancer, or cancers for which no effective standard therapy exists) allowed
Phase II portion:
- Diagnosis of cancer of the upper aerodigestive tract (head and neck, esophagus, stomach, or hepatobiliary)
- No potential curative treatment options including surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy
- No leukemia or lymphoma
- No primary CNS malignancies or CNS metastases
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Absolute granulocyte count at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
- AST and ALT no greater than 2.5 times upper limit of normal
Renal:
- Creatinine no greater than 1.6 mg/dL
Cardiovascular:
- LVEF at least 50%
- No symptomatic congestive heart failure
- No unstable angina
- No cardiac arrhythmia
Other:
- No serious concurrent medical illness that would preclude study participation
- No active infections requiring IV antibiotic therapy
- No history of allergy to platinum compounds, mannitol, or antiemetics used with study drugs
- No history of severe intolerance to fluorouracil
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- More than 4 weeks since prior immunotherapy and recovered
Chemotherapy:
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy (at least 6 weeks for nitrosoureas or mitomycin) and recovered
- No prior cumulative doxorubicin dose of more than 300 mg/m2
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- At least 2 weeks since prior radiotherapy and recovered
- At least 8 weeks since prior strontium chloride Sr 89
Surgery:
- See Disease Characteristics
- Recovered from prior surgery
Other:
- At least 4 weeks since prior sorivudine or brivudine
- No concurrent sorivudine or brivudine
- No concurrent cimetidine
- No concurrent antiretroviral therapy for HIV-positive patients
Contacts and Locations| United States, Maryland | |
| Center for Cancer Research | |
| Bethesda, Maryland, United States, 20889-5105 | |
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | |
| Bethesda, Maryland, United States, 20892-1182 | |
| United States, Virginia | |
| Naval Medical Center, Portsmouth | |
| Portsmouth, Virginia, United States, 23708-2197 | |
| Investigator: | Brian P. Monahan, MD, FACP | National Cancer Institute (NCI) |
| Study Chair: | Eva Szabo, MD | National Cancer Institute (NCI) |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00021047 History of Changes |
| Obsolete Identifiers: | NCT00015743 |
| Other Study ID Numbers: | 010172, NCI-01-C-0172, MB-NAVY-00-07, MB-NAVY-B01-008, CDR0000068741 |
| Study First Received: | July 11, 2001 |
| Last Updated: | March 7, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
stage IV gastric cancer recurrent gastric cancer stage II esophageal cancer stage III esophageal cancer stage IV esophageal cancer recurrent esophageal cancer advanced adult primary liver cancer recurrent adult primary liver cancer unresectable extrahepatic bile duct cancer recurrent extrahepatic bile duct cancer unspecified adult solid tumor, protocol specific untreated metastatic squamous neck cancer with occult primary recurrent metastatic squamous neck cancer with occult primary stage IV squamous cell carcinoma of the lip and oral cavity stage IV basal cell carcinoma of the lip |
stage IV verrucous carcinoma of the oral cavity stage IV mucoepidermoid carcinoma of the oral cavity stage IV adenoid cystic carcinoma of the oral cavity recurrent squamous cell carcinoma of the lip and oral cavity recurrent basal cell carcinoma of the lip recurrent verrucous carcinoma of the oral cavity recurrent mucoepidermoid carcinoma of the oral cavity recurrent adenoid cystic carcinoma of the oral cavity stage IV squamous cell carcinoma of the oropharynx stage IV lymphoepithelioma of the oropharynx recurrent squamous cell carcinoma of the oropharynx recurrent lymphoepithelioma of the oropharynx stage IV squamous cell carcinoma of the nasopharynx stage IV lymphoepithelioma of the nasopharynx recurrent squamous cell carcinoma of the nasopharynx |
Additional relevant MeSH terms:
|
Esophageal Diseases Esophageal Neoplasms Head and Neck Neoplasms Liver Neoplasms Stomach Neoplasms Bile Duct Neoplasms Gastrointestinal Diseases Digestive System Diseases Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Liver Diseases Stomach Diseases Biliary Tract Neoplasms |
Bile Duct Diseases Biliary Tract Diseases Epirubicin Capecitabine Carboplatin Fluorouracil Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on May 21, 2013