Gefitinib in Treating Patients With Recurrent or Metastatic Esophageal or Gastroesophageal Junction Cancer

A Phase II Trial of ZD1839 (IRESSA®) for Patients With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with recurrent or metastatic esophageal or gastroesophageal junction cancer.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: ZD1839

Detailed Description

OBJECTIVES:

Primary

• Explore the activity of single agent gefitinib, in terms of response rate, in a patient population with recurrent or metastatic esophageal or gastroesophageal junction cancer.

Secondary

• Assess the toxicity of this drug in these patients.

OUTLINE: Patients are stratified according to prior treatment (yes vs no).

Patients receive oral gefitinib once daily for at least 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed squamous cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus or gastroesophageal junction

  • Patients must have disease that is either metastatic (i.e., M1b by the definitions of the American Joint Committee on Cancer 1997 staging system) or recurrent after definitive therapy, and must be considered incurable by conventional treatments
  • Patients with small cell, or mixed small cell/non-small-cell histology are ineligible
  • Patients with lymphoma or sarcoma are also ineligible

• Disease must be measurable in at least one dimension by physical exam, x-ray, CT scan or MRI, ultrasound, or endoscopy

  • Measurable disease can be a previously irradiated lesion if disease growth has been documented in the lesion since completion of radiation therapy
  • An elevation in carcinoembryonic antigen (CEA) is not sufficient to use by itself in response assessment

PATIENT CHARACTERISTICS:

• ECOG Performance Status 0-1
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 2.0 mg/dL
• Alkaline phosphatase and AST < twice normal
• Bilirubin < twice normal
• Calcium normal
• No known severe hypersensitivity to study drug or any of its excipients
• No clinical evidence of any other uncontrolled malignancy except adequately treated basal or squamous cell skin cancer or in situ cervical cancer
• Pregnant or nursing women are ineligible
• Fertile patients must use effective contraception
• No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)

• No evidence of clinically active interstitial lung disease

  • Patients with chronic stable radiographic changes who are asymptomatic need not be excluded

PRIOR CONCURRENT THERAPY:

• Patients may not have received more than one previous systemic treatment regimen

  • Systemic treatment may have been given as part of definitive (adjuvant, neoadjuvant, concurrent, or sequential) management or for metastatic or recurrent disease
  • Previously untreated patients are also eligible
• No previous treatment with study drug or any other epidermal growth factor receptor (EGFR) antagonists
• More than 30 days since prior treatment with a non-approved or investigational drug
• At least 4 weeks must have elapsed since any surgery, radiation therapy, or chemotherapy administration
• Recovered from previous oncologic or other major surgery
• No concurrent barbiturates (e.g., phenytoin), carbamazepine, rifampicin, phenobarbital or Hypericum perforatum (St. John's wort)
• No concurrent surgery, radiation therapy, hormonal therapy, or other chemotherapy

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: ZD1839	Drug: ZD1839; ZD1839 treatment will be taken once a day PO, every day about the same time; Other Names: Gefitinib; IRESSA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Complete or Partial Response Rate of Single Agent ZD1839 in a Patient Population With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction, Using the RECIST 1.0 Criteria.	The overall response is the number of patients with the best response recorded in measurable disease (target lesions) from start to disease progression.Complete response is the number of patients with the disappearance of all target lesions. Partial response is the number of patients with larger than or equal to 30% decrease in sum of the longest diameters from baseline. Progressive disease is larger than or equal to 20% increase in sum of the longest diameters over the smallest sum observed or appearance of new lesions. Stable disease is neither PR nor PD criteria met.	at 8 weeks after initiation of treatment

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David J. Adelstein, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 20, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Estimate): January 5, 2016
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: squamous cell carcinoma of the esophagus; adenocarcinoma of the esophagus; recurrent esophageal cancer; stage IV 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; Gefitinib
• Other Study ID Numbers: CCF5538; P30CA043703 (U.S. NIH Grant/Contract); CCF-5538 (Other Identifier: Cleveland Clinic IRB); ZENECA-1839IL/0234