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

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

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Other: immunohistochemistry staining method; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 120 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Renuka Iyer, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: August 31, 2007
• First Submitted That Met QC Criteria: August 31, 2007
• First Posted (Estimate): September 3, 2007

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: March 14, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: stage II esophageal cancer; stage III esophageal cancer; squamous cell carcinoma of the esophagus; adenocarcinoma of the esophagus; stage IV esophageal cancer; stage I esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CDR0000563268; RPCI-I-62705 (Other Identifier: Roswell Park Cancer Institute)