Phase II Study in Operable Adenocarcinoma of the Esophagus to Measure Response Rate and Toxicity of Preoperative Combined Modality Paclitaxel (Taxol®, Bristol-Myers Squibb), Cisplatin (Platinol®, Abbott Laboratories), ZD1839 (IRESSA®) and Radiotherapy Followed by Postoperative ZD1839
- Determine the pathologic complete response rate in patients with resectable, locally
advanced adenocarcinoma of the esophagus or gastroesophageal junction treated with
neoadjuvant paclitaxel, cisplatin, gefitinib, and radiotherapy followed by surgery and
- Determine the survival of patients treated with this regimen.
- Determine the safety and tolerability of this regimen in these patients.
- Determine time to disease progression in patients treated with this regimen.
- Determine the plasma pharmacokinetics of unbound gefitinib in these patients.
- Conduct exploratory studies to determine if EGFR pathway component expression and
activation correlates with response to therapy and survival of these patients.
- Determine if treatment with gefitinib alters the EGFR pathway in these patients.
OUTLINE: This is a prospective study.
- Neoadjuvant therapy: Patients receive oral gefitinib beginning 14 days prior to the
start of chemoradiotherapy and continuing until 7 days prior to surgery (10-12 weeks).
Patients also receive paclitaxel IV over 1 hour and cisplatin IV over 2-3 hours on days
1, 8, 15, 22, and 29. Patients also undergo radiotherapy 5 days a week for 5 weeks.
- Surgery: Patients undergo surgical resection 4-6 weeks after the completion of
- Adjuvant therapy: Patients receive gefitinib once a day beginning 2-8 weeks after
surgery and continuing for up to 1 year in the absence of disease progression or
Blood samples are obtained at baseline and periodically during study for pharmacokinetic
studies. Tumor tissue samples are obtained by core biopsy at baseline for biomarker
correlative studies. Samples are analyzed by IHC to measure expression and activation of
EGFR-signaling pathway biomarkers in pretreatment esophageal tumor tissue, including EGFR
and phosphorylated (p)-EGFR, ERK and p-ERK, Akt and p-Akt, p70s6k and p-p70s6k, and p27.
After completion of study therapy, patients are followed periodically for at least 5 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response rate to the neoadjuvant regimen
Arlene A. Forastiere, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Institutional Review Board
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|