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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer; Adenocarcinoma of the Gastroesophageal Junction
• Intervention / Treatment: Procedure: quality-of-life assessment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefitinib 500mg once daily	Procedure: quality-of-life assessment
Placebo Comparator: Placebo; Gefitinib 500mg once daily	Procedure: quality-of-life assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	4, 8, 12, 16 weeks then every 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity and safety	4, 8, 12, 16 weeks then every 8 weeks
Quality of life	4, 8 and 12 weeks
Progression-free survival	4, 8, 12, 16 weeks then every 8 weeks

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: David Ferry, MD, New Cross Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Estimate): November 29, 2012
• Last Update Submitted That Met QC Criteria: November 28, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: squamous cell carcinoma of the esophagus; adenocarcinoma of the esophagus; stage IIB esophageal cancer; adenocarcinoma of the gastroesophageal junction; stage IIIA esophageal cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer; recurrent esophageal cancer; stage IV esophageal cancer; stage IIA esophageal cancer; stage IA esophageal cancer; stage IB esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms
• Other Study ID Numbers: CDR0000689080; OXFORD-COG; UO-COG; EUDRACT-2007-005391-13; ISRCTN-29580179; AZ-D7913L00059; EU-21085