Erlotinib and Radiation Therapy in Treating Older Patients With Stage I, Stage II, Stage III, or Stage IV Esophageal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Erlotinib 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 erlotinib together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving erlotinib together with radiation therapy works in treating older patients with stage I, stage II, stage III, or stage IV esophageal cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Assess the overall survival of older patients with stage I-IV squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction treated with erlotinib hydrochloride in combination with radiotherapy. Secondary Assess the proportion of patients achieving mucosal complete response after treatment with this regimen. Determine the progression-free survival of patients treated with this regimen. Assess the effect of this regimen on dysphagia control, performance status, and overall quality of life of these patients. Investigate the correlation between smoking status and overall survival of these patients. To correlate the Epidermal growth factor receptor (EGFR) and phosphor Epidermal growth factor receptor (pEGFR) expression by IHC and EGFR mutation status with clinical outcomes. OUTLINE: This is a multicenter study. Patients receive oral erlotinib hydrochloride once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo external beam radiotherapy 5 days a week in weeks 1-4 or 5 days a week for the first 5.5 weeks. Tumor tissue samples are analyzed by IHC for the expression of E-cadherin, P-cadherin, vimentin, cytokeratin, phospho-S6, and Ki67. After completion of study treatment, patients are followed at 30 days and annually thereafter.

Official Title
-----------------
Phase II Study of Erlotinib (Tarceva®) and Radiotherapy for Elderly Patients With Esophageal Carcinoma

Conditions
-----------------
Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: erlotinib hydrochloride
* Other: immunohistochemistry staining method
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Biopsy-proven primary squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction GE junction tumors with 50% or more tumor located in the esophagus determined by radiologic or endoscopic evaluation Stage I-IVA disease determined by CT scan or MRI of the chest and abdomen Stage IVB disease allowed if metastases to distant regional lymph nodes (celiac or cervical) only and no other sites Not a surgical candidate and ineligible for chemotherapy due to any of the following: Neuropathy Cardiac disease Performance status 2 General overall condition felt by the investigator to be a contraindication to platinum-based therapy Bronchoscopy with biopsy and cytology required if primary esophageal cancer is < 26 cm from incisors No evidence of clinically active interstitial lung disease (patients who are asymptomatic with chronic, stable, radiographic lung changes allowed) PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 4 months WBC ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count > 100,000/mm³ Bilirubin ≤ 1.3 mg/dL ALT and AST ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN No prior malignancies except basal cell or squamous cell skin cancer, in situ cervical cancer, or superficial transitional cell bladder cancer, unless diagnosed and/or treated > 2 years prior to current study and are without evidence of recurrence No history of allergy to erlotinib or any of its excipients No serious, uncontrolled, concurrent infection No clinically serious, uncontrolled medical conditions that the investigator feels might compromise study participation No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome No unwillingness to participate or inability to comply with the protocol for the duration of the study PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for this tumor No prior resection or attempted resection of esophageal cancer No prior anti-epidermal growth factor receptor therapy (unless given in an adjuvant setting and completed at least 12 months earlier) No participation in any investigational drug study within the past 4 weeks No HIV-positive patients receiving antiretroviral therapy No concurrent CYP3A4/5 inducers or inhibitors

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Erlotinib<br>Patients receive oral erlotinib hydrochloride once daily for 1 year | Drug: erlotinib hydrochloride<br>* Oral<br>Other: immunohistochemistry staining method<br>* Correlative Study<br>Radiation: radiation therapy<br>* Radiation Treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | Response assessment by CT scans and upper endoscopy performed between 4-8 weeks after completion of radiation. Complete Response (CR) is defined as absence of viable tumor in endoscopic evaluation post chemoradiation, with four-quadrant biopsies taken at 1 cm intervals throughout length of original tumor. | 4-8 weeks after completion of radiation. | 
| Progresssion-Free Survival | Progression is defined as at least a 20% increase in the sum of long distance of target lesions taking as reference the smallest sum long distance recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | Every 3 months, up to 5 years | 
| Effect of Study Therapy on Overall Quality of Life as Assessed by FACT-E Scale | Functional Assessment of Cancer Therapy-Esophagus (FACT-E) is a health-related quality of life instrument validated in esophageal cancer patients. All of the scales and single-item measures range in score from 0 to 4. The ranges of average quality of life scores was from 0 to 4 and was adjusted as lower scores indicate better outcomes | Baseline and Week 3 | 
| Correlation of Smoking Status With Overall Survival |  | 5 years | 
| Response by Epidermal Growth Factor Receptor (EGFR) Expression |  | Radiologic evaluation every 3 months, up to 5 years | 
| Response by Phosphor Epidermal Growth Factor Receptor (pEGFR) Expression |  | Radiologic evaluation every 3 months, up to 5 years | 
| Response by EGFR Mutation Status |  | Radiologic evaluation every 3 months, up to 5 years | 

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