Paclitaxel, Cisplatin, Gefitinib, and Radiation Therapy Followed by Surgery and Gefitinib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction That Can Be Removed By Surgery
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving gefitinib after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving paclitaxel, cisplatin, gefitinib, and radiation therapy followed by surgery and gefitinib works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction that can be removed by surgery.
|Esophageal Cancer||Drug: cisplatin Drug: gefitinib Drug: paclitaxel Genetic: gene expression analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Procedure: adjuvant therapy Procedure: biopsy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Pathologic complete response rate to the neoadjuvant regimen [ Time Frame: 5 years ]
- Toxicity as assessed by NCI CTC v2.0 [ Time Frame: 5 years ]
- Safety [ Time Frame: 5 years ]
- Time to progression [ Time Frame: 5 years ]
- Survival [ Time Frame: 5 years ]
- Correlation between EGFR pathway component expression and activation with pathologic complete response and survival [ Time Frame: 5 years ]
|Study Start Date:||April 2005|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
- 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 adjuvant gefitinib.
- 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 neoadjuvant therapy.
- 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 unacceptable toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00493025
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||Arlene A. Forastiere, MD||Sidney Kimmel Comprehensive Cancer Center|