Esophageal Cancer Clinical Trial
Oxaliplatin, Gefitinib, and Radiation Therapy in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer
Summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining oxaliplatin and gefitinib with radiation therapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin when given together with gefitinib and radiation therapy and to see how well they work in treating patients with locally advanced or metastatic esophageal cancer.
Full Description
OBJECTIVES:
Primary
Determine the maximum tolerated dose of oxaliplatin when administered with gefitinib and radiotherapy in patients with locally advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction. (Phase I)
Determine the response rate in patients treated with this regimen. (Phase II)
Secondary
Determine time to tumor progression and median survival in patients treated with this regimen.
Determine quality of life in patients treated with this regimen.
Determine the safety of this regimen in these patients.
OUTLINE: This is a phase I, open-label, dose-escalation study of oxaliplatin followed by a phase II study.
Phase I: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29. Beginning on day 1, patients undergo radiotherapy once daily, 5 days a week, for 5.5 weeks. Patients also receive oral gefitinib once daily on days 1-365. Treatment continues in the absence of disease progression or unacceptable toxicity Approximately 3-6 weeks after the completion of chemoradiotherapy, patients are evaluated. Some patients undergo surgical resection* and possibly receive a second course of oxaliplatin (IV over 2 hours on days 1, 15, and 29) 4-8 weeks after surgery. If surgery is not indicated, some patients may receive an additional course of oxaliplatin.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose 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.
Phase II: Patients receive oxaliplatin, gefitinib, and radiotherapy as in phase I at the MTD. Some patients then either undergo surgical resection* and/or begin a second course of oxaliplatin as in phase I.
NOTE: *Oral gefitinib is discontinued ≥ 7 days before surgery and is restarted when the patient has recovered.
Quality of life is assessed at baseline, 5-6 weeks, and then every 2-3 months for 1 year.
Patients are followed every 2-3 months for 1 year.
PROJECTED ACCRUAL: Approximately 15-45 patients (3-12 for phase I and 12-33 for phase II) will be accrued for this study within 2 years.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal (GE) junction
Locally advanced or metastatic disease by clinical staging, including esophagogastroduodenoscopy and esophageal ultrasound
Stage T2, N0 disease and beyond
Bulk of tumor must be in the esophagus of patients with GE junction tumor
Bronchoscopy is required if primary esophageal tumor is < 26 cm from the incisors
No brain metastases
PATIENT CHARACTERISTICS:
Age
Over 18
Performance status
ECOG 0-1
Life expectancy
At least 4 months
Hematopoietic
WBC ≥ 3,000/mm^3
Granulocyte count ≥ 1,500/mm^3
Platelet count > 100,000/mm^3
Hepatic
Bilirubin normal
ALT and AST ≤ 2.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Renal
Not specified
Cardiovascular
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Pulmonary
No clinically active interstitial lung disease
Patients with chronic stable asymptomatic radiographic changes are eligible
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation
No peripheral neuropathy ≥ grade II
No severe hypersensitivity to gefitinib or any of its excipients
No history of allergy to platinum-based compounds or antiemetics administered with protocol-directed chemotherapy
No active or ongoing infection
No other uncontrolled illness
No other significant clinical disorder or laboratory finding that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
No concurrent colony-stimulating factors during course 1 of study therapy
Chemotherapy
More than 4 weeks since prior chemotherapy
Endocrine therapy
Concurrent steroid therapy allowed
Radiotherapy
More than 4 weeks since prior radiotherapy
Surgery
Not specified
Other
More than 30 days since prior non-approved or investigational drugs
No concurrent administration of any of the following:
Phenytoin
Carbamazepine
Rifampin
Barbiturates
Highly-active antiretroviral therapy (HAART)
Hypericum perforatum (St. John's wort)
No other concurrent investigational agents or therapy
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There is 1 Location for this study
Buffalo New York, 14263, United States
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