Oxaliplatin, Gefitinib, and Radiation Therapy in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer

October 5, 2015 updated by: Roswell Park Cancer Institute

ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining oxaliplatin and gefitinib with radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin when given together with gefitinib and radiation therapy and to see how well they work in treating patients with locally advanced or metastatic esophageal cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of oxaliplatin when administered with gefitinib and radiotherapy in patients with locally advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction. (Phase I)
  • Determine the response rate in patients treated with this regimen. (Phase II)

Secondary

  • Determine time to tumor progression and median survival in patients treated with this regimen.
  • Determine quality of life in patients treated with this regimen.
  • Determine the safety of this regimen in these patients.

OUTLINE: This is a phase I, open-label, dose-escalation study of oxaliplatin followed by a phase II study.

  • Phase I: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29. Beginning on day 1, patients undergo radiotherapy once daily, 5 days a week, for 5.5 weeks. Patients also receive oral gefitinib once daily on days 1-365. Treatment continues in the absence of disease progression or unacceptable toxicity Approximately 3-6 weeks after the completion of chemoradiotherapy, patients are evaluated. Some patients undergo surgical resection* and possibly receive a second course of oxaliplatin (IV over 2 hours on days 1, 15, and 29) 4-8 weeks after surgery. If surgery is not indicated, some patients may receive an additional course of oxaliplatin.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive oxaliplatin, gefitinib, and radiotherapy as in phase I at the MTD. Some patients then either undergo surgical resection* and/or begin a second course of oxaliplatin as in phase I.

NOTE: *Oral gefitinib is discontinued ≥ 7 days before surgery and is restarted when the patient has recovered.

Quality of life is assessed at baseline, 5-6 weeks, and then every 2-3 months for 1 year.

Patients are followed every 2-3 months for 1 year.

PROJECTED ACCRUAL: Approximately 15-45 patients (3-12 for phase I and 12-33 for phase II) will be accrued for this study within 2 years.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal (GE) junction

    • Locally advanced or metastatic disease by clinical staging, including esophagogastroduodenoscopy and esophageal ultrasound

      • Stage T2, N0 disease and beyond

    • Bulk of tumor must be in the esophagus of patients with GE junction tumor

      • Bronchoscopy is required if primary esophageal tumor is < 26 cm from the incisors
  • No brain metastases

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • ECOG 0-1

Life expectancy

  • At least 4 months

Hematopoietic

  • WBC ≥ 3,000/mm^3
  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count > 100,000/mm^3

Hepatic

  • Bilirubin normal
  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN

Renal

  • Not specified

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Pulmonary

  • No clinically active interstitial lung disease

    • Patients with chronic stable asymptomatic radiographic changes are eligible

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation
  • No peripheral neuropathy ≥ grade II
  • No severe hypersensitivity to gefitinib or any of its excipients
  • No history of allergy to platinum-based compounds or antiemetics administered with protocol-directed chemotherapy
  • No active or ongoing infection
  • No other uncontrolled illness
  • No other significant clinical disorder or laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent colony-stimulating factors during course 1 of study therapy

Chemotherapy

  • More than 4 weeks since prior chemotherapy

Endocrine therapy

  • Concurrent steroid therapy allowed

Radiotherapy

  • More than 4 weeks since prior radiotherapy

Surgery

  • Not specified

Other

  • More than 30 days since prior non-approved or investigational drugs

  • No concurrent administration of any of the following:

    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Barbiturates
    • Highly-active antiretroviral therapy (HAART)
    • Hypericum perforatum (St. John's wort)
  • No other concurrent investigational agents or therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose (phase I)
Response (phase II)

Secondary Outcome Measures

Outcome Measure
Quality of life
Survival
Safety and toxicity
Immunohistochemistry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Investigators

  • Principal Investigator: Milind Javle, MD, Roswell Park Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

May 1, 2006

Study Registration Dates

First Submitted

October 6, 2004

First Submitted That Met QC Criteria

October 7, 2004

First Posted (Estimate)

October 8, 2004

Study Record Updates

Last Update Posted (Estimate)

October 6, 2015

Last Update Submitted That Met QC Criteria

October 5, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I 04603
  • RPCI-I-04603
  • ZENECA-IRUSIRES0303

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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