Clinical trial NCT00021047: Epirubicin, Carboplatin, and Capecitabine in Treating Patients With Unresectable Locally Advanced, Metastatic, or Recurrent Solid Tumor
Official title: A Phase I/II Trial of Epirubicin, Carboplatin & Capecitabine in Adult Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Extrahepatic Bile Duct Cancer
Gastric Cancer
Head and Neck Cancer
Liver Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
recurrent lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
stage IV salivary gland cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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 criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Center for Cancer Research
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Portsmouth
country: United States
facility: Naval Medical Center, Portsmouth
state: Virginia
Study officials:
affiliation: National Cancer Institute (NCI)
name: Brian P. Monahan, MD, FACP
affiliation: National Cancer Institute (NCI)
name: Eva Szabo, MD
role: STUDY_CHAIR
References: