RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving erlotinib after chemoradiotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of adjuvant erlotinib after completing chemoradiotherapy in treating patients who have locally advanced squamous cell carcinoma (cancer) of the head and neck.

Condition	Treatment or Intervention	Phase
Head and Neck Cancer	Drug: erlotinib  Procedure: adjuvant therapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

OBJECTIVES: Primary

• Determine the recommended dose of adjuvant erlotinib after the completion of chemoradiotherapy in patients with stage III, IVA, or IVB squamous cell carcinoma of the head and neck.
• Determine the toxicity of this drug in these patients.
• Determine the effects of this drug on plasma and urinary angiogenic factors (specifically vascular endothelial growth factor receptor [VEGFR], VEGFR1, VEGFR2, and basic fibroblast growth factor levels) in these patients.
• Compare the disease-free survival of patients treated with this drug after chemoradiotherapy vs historical control patients treated with chemoradiotherapy alone.
• Correlate levels of angiogenic factors with initial blood vessel concentration in the tumor and the presence or absence of EGFRvIII mutation in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral erlotinib once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 8 patients are treated at that dose level.

Patients are followed at 4 weeks, every 12 weeks for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck
• Stage III, IVA, or IVB
• Must have completed cisplatin- or carboplatin-based chemoradiotherapy within the past 4-12 weeks
• Prior radiotherapy must have been given with a radical intent with receipt of at least 90% of planned dose
• No evidence of disease or presence of inoperable minimal residual disease, defined by 1 of the following:
• Complete response at primary tumor site and nodes (with or without nodal surgery after chemoradiotherapy)
• Negative lymph node status (by physical or radiological exam) AND persistent tumefaction less than 25% of original tumor size or residual mass due to scarring
• Tumor tissue samples available for EGFRvIII mutation analysis
• No known brain metastasis

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• ALT/AST < 2 times upper limit of normal (ULN)
• Bilirubin < ULN (unless due to Gilbert’s syndrome)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• No history of cardiac disease
• No uncontrolled high blood pressure
• No unstable angina
• No congestive heart failure

Ophthalmic

• No history of severe dry eye syndrome, Sjögren’s syndrome, or keratoconjunctivitis sicca
• No severe exposure keratopathy
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
• No disorder that might increase the risk for epithelium-related complication (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
• No congenital abnormality (e.g., Fuch’s dystrophy)
• No ocular inflammation or infection

Gastrointestinal

• Able to take oral medication
• No gastrointestinal (GI) tract disease requiring IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No active peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious active infection
• No other serious underlying medical condition that would preclude study participation
• No prior allergic reaction to compounds of similar chemical or biological composition to erlotinib
• No other malignancy with the past 5 years except adequately treated non-melanoma skin cancer (unless in the same area treated with radical radiotherapy) or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics
• No prior surgical procedure affecting absorption
• No concurrent ophthalmic surgery

Other

• More than 4 weeks since other prior investigational drugs
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance with respect to INR
• Concurrent nasogastric or gastrostomy tube feeding for dysphagia allowed provided there is no evidence of significant residual mucositis (i.e., > grade 1)

Canada, Ontario
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L-4M1,  Canada; Recruiting

Study chairs or principal investigators

Denis Soulieres, MD,  Study Chair,  Centre Hospitalier de l'Universite de Montreal   

Study ID Numbers:  CDR0000353485; CAN-NCIC-HN5; ROCHE-CAN-NCIC-HN5
Record last reviewed:  May 2004
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079053
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18