Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	UCHSC-01460 NCI-4551, NCT00033449, 4551

Objectives

1. Determine the maximum tolerated dose of gefitinib in combination with radiotherapy with or without cisplatin in patients with previously untreated, locally advanced squamous cell carcinoma of the head and neck.
2. Determine the dose-dependent local and/or systemic toxic effects of these regimens in these patients.
3. Determine the feasibility and toxicity profile of protracted continuous daily dosing of gefitinib after completion of radiotherapy in these patients.
4. Determine the response rate, relapse-free survival rate, and overall survival rate in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed locally advanced squamous cell carcinoma of the head and neck involving the oral cavity, oropharynx, hypopharynx, or supraglottic or glottic larynx
  • Unresectable disease
    • Medically inoperable resectable disease allowed
  • Stage III or IV
    • No distant metastases



• Only patients with intermediate stage disease (T1-2, N1-N2a or T3, N0-1) are eligible for radiotherapy alone with gefitinib

Prior/Concurrent Therapy:

Biologic therapy:

• No prior monoclonal antibodies with potential epidermal growth factor receptor (EGFR) binding therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• No prior surgery except biopsy

Other:

• No prior anti-EGFR therapy including prior tyrosine kinase inhibitors
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent commercial or investigational agents or therapies intended to treat the malignancy

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy:

• More than 6 months

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin normal
• AST and ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiac:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Medically suitable to withstand a course of definitive radiotherapy
• No ongoing or active infection
• No other malignancy within the past 3 years except basal cell skin cancer or carcinoma in situ of the cervix
• No prior allergic reactions to compounds of similar chemical or biological composition to gefitinib or other study agents
• No uncontrolled concurrent medical or psychiatric illness or social situation that would preclude study participation

Expected Enrollment

A total of 30 patients will be accrued for this study.

Outcomes

Safety profile of gefitinib
Maximum tolerated dose as assessed by dose-limiting toxicities from 0-2 years
Dose-dependent local and/or systemic toxicity as assessed by CTC v 2.0 from 0-2 years
Feasibility and toxicity profile as assessed by CTC v 2.0 at 2 years post-radiotherapy

Response rates, relapse-free survival rates, and overall survival rates as measured by radiological assessments every 4 months for 2 years, at 2 years, and every 6 months for years 3-5
Biological effects as assessed by biological analyses after 1 week of treatment, weekly during treatment, and at 8 weeks post-radiotherapy

Outline

This is a multicenter, dose-escalation study of gefitinib.

All patients receive oral gefitinib once daily beginning at least 7 days before and continuing throughout radiotherapy or chemoradiotherapy in the absence of disease progression or unacceptable toxicity. Patients are entered into 1 of 5 levels.

• Level I: Patients undergo concurrent boost radiotherapy 5 days per week comprising once daily radiotherapy for 3.5 weeks followed by twice daily radiotherapy for 2.5 weeks.



• Level II: Patients receive escalated dose of gefitinib and undergo radiotherapy as in level I.



• Level III: Patients receive original dose of gefitinib, undergo standard fractionation radiotherapy comprising once daily radiotherapy 5 days per week for 7 weeks, and receive cisplatin IV over 30-60 minutes at the beginning of each week of radiotherapy.



• Level IV: Patients receive escalated dose of gefitinib as in level II and undergo radiotherapy and chemotherapy as in level III.



• Level V: Patients receive the maximum tolerated dose (MTD) of gefitinib, radiotherapy 5 days a week for 6 weeks, and chemotherapy as in level III.

Patients with clinical or radiologic evidence of residual disease are required to undergo neck dissection approximately 8 weeks after completion of radiotherapy or chemoradiotherapy.

Patients resume oral gefitinib daily beginning 8 weeks after the completion of radiotherapy or chemoradiotherapy (12 weeks for patients who undergo neck dissection) and continuing for 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients are enrolled sequentially beginning at level I until the MTD of gefitinib is determined. The MTD is the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Twelve additional patients receive the MTD of gefitinib in combination with radiotherapy with or without cisplatin.

Patients are followed every 6 months for at least 5 years.

Chen C, Kane M, Song J, et al.: Phase I trial of gefitinib in combination with radiation or chemoradiation for patients with locally advanced squamous cell head and neck cancer. J Clin Oncol 25 (31): 4880-6, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

University of Colorado Cancer Center at UC Health Sciences Center

David Raben, MD, Protocol chair		Ph: 720-848-0116; 800-473-2288 Email: david.raben@uchsc.edu

Registry Information
Official Title		A Phase I Study Of ZD 1839 In Combination With Radiation And Chemotherapy In Locally Advanced Sqamous Cell Carcinoma Of The Head And Neck
Trial Start Date		2002-03-28
Registered in ClinicalTrials.gov		NCT00033449
Date Submitted to PDQ		2002-02-05
Information Last Verified		2006-09-17
NCI Grant/Contract Number		CA46934

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