ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates
18 Years
N/A
Both
Esophageal Cancer
Trial Information
ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (phase I)
Safety Issue:
Yes
Principal Investigator
Milind Javle, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Federal Government
Study ID:
I 04603
NCT ID:
NCT00093652
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
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
