Oxaliplatin, Gefitinib, and Radiation Therapy in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer
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.
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates|
- Maximum tolerated dose (phase I) [ Designated as safety issue: Yes ]
- Response (phase II) [ Designated as safety issue: No ]
- Survival [ Designated as safety issue: No ]
- Quality of life [ Designated as safety issue: No ]
- Safety and toxicity [ Designated as safety issue: Yes ]
- Immunohistochemistry [ Designated as safety issue: No ]
|Study Start Date:||May 2003|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
- 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)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00093652
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Principal Investigator:||Milind Javle, MD||Roswell Park Cancer Institute|