Gefitinib in Treating Patients With Esophageal Cancer That is Progressing After Chemotherapy

Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Gefitinib (Iressa®) Versus Placebo in Esophageal Cancer Progressing After Chemotherapy

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether gefitinib is more effective than a placebo in treating esophageal cancer.

PURPOSE: This randomized phase III trial is studying gefitinib to see how well it works compared with a placebo in treating patients with esophageal cancer that is progressing after chemotherapy.

OBJECTIVES:

Primary

• To assess whether gefitinib vs placebo will improve overall survival of patients with esophageal or gastroesophageal junction cancer.

Secondary

• To assess the toxicity of gefitinib monotherapy in these patients.
• To assess whether gefitinib vs placebo will have a significant positive or negative impact upon quality of life of these patients.
• To assess the impact gefitinib vs placebo will have on progression-free survival of these patients.

OUTLINE: This is a multicenter study.

• Arm A: Patients receive oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
• Arm B: Patients receive oral placebo once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood samples are collected for genetic and translational studies. Patient's quality of life is assessed at baseline and periodically during the study with completion of EORTC Quality of Life Questionnaire (QLQ-C30) version 3.0.

After completion of study treatment, patients are followed up every 8 weeks.

DISEASE CHARACTERISTICS:

• Histologically confirmed esophageal cancer or gastroesophageal junction tumor including the following subtypes:

  • Adenocarcinoma
  • Squamous cell cancer
  • Poorly differentiated epithelial malignancy
  • Gastroesophageal junction with Siewert type I or II tumors

• Failure after no more than 2 prior chemotherapy regimens and 1 chemoradiation course

• Measurable or evaluable disease by CT scan

• Patients with brain metastases must be stable and have received cranial irradiation prior to entry

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Serum bilirubin ≤ 3 times the upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN (≤ 5 x in presence of liver metastases)
• Able to take oral tablets (whole or dispersed)
• No evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic allowed)
• No known severe hypersensitivity to gefitinib or any of the excipients of this product
• No prior other malignancy likely to confound results or interfere with gefitinib therapy
• No medical condition considered to interfere with the safe participation in the trial
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No chemotherapy (including oral) within the past 6 weeks
• No radiotherapy to site of measurable or evaluable disease within the past 4 weeks
• No other concurrent cytotoxic chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids) or experimental medications