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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00524121
• Other study ID #: CDR0000563268
• Secondary ID: RPCI-I-62705
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2007
• Last updated: February 19, 2015
• Start date: March 2006
• Est. completion date: October 2011

Study information

• Verified date: February 2015
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• erlotinib hydrochloride
Oral

Other:
• immunohistochemistry staining method
Correlative Study

Radiation:
• radiation therapy
Radiation Treatment

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		5 years	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	Correlation of Smoking Status With Overall Survival		5 years	No
Secondary	Response by Epidermal Growth Factor Receptor (EGFR) Expression		Radiologic evaluation every 3 months, up to 5 years	No
Secondary	Response by Phosphor Epidermal Growth Factor Receptor (pEGFR) Expression		Radiologic evaluation every 3 months, up to 5 years	No
Secondary	Response by EGFR Mutation Status		Radiologic evaluation every 3 months, up to 5 years	No