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

NCT ID: NCT00093652

Last Updated: 2015-10-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31

Brief Summary

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.

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.

Conditions

Esophageal Cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

gefitinib

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Principal Investigators

Milind Javle, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

References

Javle M, Pande A, Iyer R, Yang G, LeVea C, Wilding G, Black J, Nava H, Nwogu C. Pilot study of gefitinib, oxaliplatin, and radiotherapy for esophageal adenocarcinoma: tissue effect predicts clinical response. Am J Clin Oncol. 2008 Aug;31(4):329-34. doi: 10.1097/COC.0b013e318161dc04.

Reference Type: RESULT

PMID: 18845990 (View on PubMed)

Other Identifiers

RPCI-I-04603

Identifier Type: -

Identifier Source: secondary_id

ZENECA-IRUSIRES0303

Identifier Type: -

Identifier Source: secondary_id

I 04603

Identifier Type: -

Identifier Source: org_study_id