Oxaliplatin, Gefitinib, and Radiation Therapy in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Esophageal Cancer |
Drug: gefitinib Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | ZD1839 (IRESSA®) With Oxaliplatin and Radiotherapy for Esophageal Carcinoma. A Phase I/II Study With Biologic Correlates |
- Maximum tolerated dose (phase I) [ Designated as safety issue: Yes ]
- Response (phase II) [ Designated as safety issue: No ]
- Survival [ Designated as safety issue: No ]
- Quality of life [ Designated as safety issue: No ]
- Safety and toxicity [ Designated as safety issue: Yes ]
- Immunohistochemistry [ Designated as safety issue: No ]
| Study Start Date: | May 2003 |
| Primary Completion Date: | May 2006 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New York | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263-0001 | |
| Principal Investigator: | Milind Javle, MD | Roswell Park Cancer Institute |
More Information
Additional Information:
Publications:
| ClinicalTrials.gov Identifier: | NCT00093652 History of Changes |
| Other Study ID Numbers: | I 04603, RPCI-I-04603, ZENECA-IRUSIRES0303 |
| Study First Received: | October 6, 2004 |
| Last Updated: | January 30, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Roswell Park Cancer Institute:
|
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 |
Additional relevant MeSH terms:
|
Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Digestive System Diseases Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Head and Neck Neoplasms |
Oxaliplatin Gefitinib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013