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

Phase 1/Phase 2
18 Years
Not Enrolling
Esophageal Cancer

Thank you

Trial Information

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



- 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)


- Determine time to tumor progression and median survival in patients treated with this

- 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.

Inclusion Criteria


- 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

- No brain metastases



- Over 18

Performance status

- ECOG 0-1

Life expectancy

- At least 4 months


- WBC ≥ 3,000/mm^3

- Granulocyte count ≥ 1,500/mm^3

- Platelet count > 100,000/mm^3


- Bilirubin normal

- ALT and AST ≤ 2.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN


- Not specified


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia


- No clinically active interstitial lung disease

- Patients with chronic stable asymptomatic radiographic changes are eligible


- 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


Biologic therapy

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


- More than 4 weeks since prior chemotherapy

Endocrine therapy

- Concurrent steroid therapy allowed


- More than 4 weeks since prior radiotherapy


- Not specified


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (phase I)

Safety Issue:


Principal Investigator

Milind Javle, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Federal Government

Study ID:

I 04603



Start Date:

May 2003

Completion Date:

Related Keywords:

  • Esophageal Cancer
  • adenocarcinoma of the esophagus
  • recurrent esophageal cancer
  • stage II esophageal cancer
  • stage III esophageal cancer
  • stage IV esophageal cancer
  • squamous cell carcinoma of the esophagus
  • Esophageal Diseases
  • Esophageal Neoplasms



Roswell Park Cancer Institute Buffalo, New York  14263