Clinical trial NCT00524121: Erlotinib and Radiation Therapy in Treating Older Patients With Stage I, Stage II, Stage III, or Stage IV Esophageal Cancer
Official title: Phase II Study of Erlotinib (Tarceva®) and Radiotherapy for Elderly Patients With Esophageal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: 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
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2007-09-03
Enrollment: 22
Sex: ALL
Minimum age (years): 65
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival
timeFrame: 5 years
Secondary outcomes:
measure: Complete Response
timeFrame: 4-8 weeks after completion of radiation.
measure: Progresssion-Free Survival
timeFrame: Every 3 months, up to 5 years
measure: Effect of Study Therapy on Overall Quality of Life as Assessed by FACT-E Scale
timeFrame: Baseline and Week 3
measure: Correlation of Smoking Status With Overall Survival
timeFrame: 5 years
measure: Response by Epidermal Growth Factor Receptor (EGFR) Expression
timeFrame: Radiologic evaluation every 3 months, up to 5 years
measure: Response by Phosphor Epidermal Growth Factor Receptor (pEGFR) Expression
timeFrame: Radiologic evaluation every 3 months, up to 5 years
measure: Response by EGFR Mutation Status
timeFrame: Radiologic evaluation every 3 months, up to 5 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Renuka Iyer, MD
role: PRINCIPAL_INVESTIGATOR
References: