ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates
- 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
- 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.
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (phase I)
Milind Javle, MD
Roswell Park Cancer Institute
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|