Gefitinib, Cisplatin, Irinotecan, and Radiation Therapy Before Surgery in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving gefitinib together with chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase I/II trial is studying the side effects of gefitinib when given together with cisplatin, irinotecan, and radiation therapy before surgery and to see how well they work in treating patients with esophageal cancer or gastroesophageal junction cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Evaluate the pathologic response (complete and partial) in patients with resectable esophageal or gastroesophageal junction cancer treated with neoadjuvant gefitinib, cisplatin, irinotecan hydrochloride, and radiotherapy followed by surgical resection. Secondary Assess the safety and toxicity of this regimen in these patients. Evaluate objective tumor response in patients treated with this regimen. Determine the rate of complete resection in patients treated with this regimen. Determine surgical morbidity and mortality in patients treated with this regimen. OUTLINE: This is an open-label study. Induction phase: Patients receive oral gefitinib once daily on days 1-14. Patients with stable or responding disease proceed to neoadjuvant chemoradiotherapy. Neoadjuvant chemoradiotherapy: Patients receive gefitinib as in the induction phase beginning in week 4 and continuing through the last day of radiotherapy. Patients also receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over 30 minutes on days 22, 29, 43, and 50 and undergo radiotherapy once daily, 5 days a week, for 5 weeks (total of 25 doses). Surgery: Within 4-8 weeks after completion of neoadjuvant chemoradiotherapy, patients with stable or responding disease undergo an esophagectomy and lymph node dissection. Patients with a progressive or unresectable disease are removed from the study. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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A Phase I/II Study to Evaluate Safety and Efficacy in Patients Who Have Resectable Esophageal Cancer and Are Treated With Neoadjuvant Cisplatin, Irinotecan (CPT-11) ZD1839 (IRESSA), and Radiotherapy Followed by Surgical Resection

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gefitinib
* Drug: irinotecan hydrochloride
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma (AC) or squamous cell carcinoma of the esophagus AC of the gastroesophageal junction allowed Tumor must be considered surgically resectable (T1-3, NX) No early-stage cancer (T1, N0) The following lymph node (LN) criteria are considered acceptable: Regional thoracic LN metastases (N1) LN metastases levels 15 to 20 measured as ≤ 1.5 cm by CT scan Supraclavicular LN not palpable on clinical examination measured as ≤ 1.5 cm by CT scan No distant metastases (M0) PATIENT CHARACTERISTICS: Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Hemoglobin ≥ 9.0 g/dL Creatinine clearance ≥ 50 mL/min Creatinine serum level ≤ CTC grade 2 Bilirubin ≤ 2 times upper limit of normal (ULN) AST < 3 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment No known severe hypersensitivity to gefitinib or any of its excipients No evidence (except asymptomatic chronic stable radiographic changes) of clinically active interstitial lung disease No pulmonary fibrosis, Gilbert's disease, uncontrolled diabetes mellitus, or unstable angina No New York Heart Association class III or IV heart disease No other concurrent malignancies or malignancies diagnosed within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix No serious active or uncontrolled infection, systemic disease, psychiatric illness, or other medical condition that would preclude study participation No evidence of any significant clinical disorder or laboratory finding that would preclude study participation PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for esophageal cancer No prior radiotherapy that would overlap the study treatment fields Recovered from prior major surgery No nonapproved or investigational drugs within the past 30 days No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: gefitinib|nan|
|Drug: irinotecan hydrochloride|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response (complete and partial) post-operatively |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity post-operatively |  |  | 
| Response rate 2 weeks into treatment, pre-operatively, and post-operatively |  |  | 
| Completeness of resection post-operatively |  |  | 
| Surgical morbidity and mortality post-operatively |  |  | 
| Compare the effects of gefitinib on biomarkers that effect EGF signaling and genomic composition of tumor samples before and after treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer