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

Alternate Title

Adjuvant Erlotinib After Completing Chemoradiotherapy in Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	Other, Pharmaceutical / Industry	CAN-NCIC-HN5 ROCHE-CAN-NCIC-HN5, NCT00079053, HN5

Objectives

Primary

1. 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.
2. Determine the toxicity of this drug in these patients.
3. 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.
4. Compare the disease-free survival of patients treated with this drug after chemoradiotherapy vs historical control patients treated with chemoradiotherapy alone.
5. 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.

Entry 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

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)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

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

Outcomes

Toxicity/feasibility assessed by NCI CTC v2.0 at the end of course 1
Recommended phase II dose at the end of course 1

Correlative studies (archival and prospective) at accrual completion
Disease-free survival

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.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Denis Soulieres, MD, MSC, Protocol chair		Ph: 514-890-8200 ext. 27066 Email: denis.soulieres.chum@ssss.gouv.qc.ca

Registry Information
Official Title		A Phase I Study of Adjuvant OSI-774 (Tarceva®) in Patients Following Combined Chemo-Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Trial Start Date		2003-11-05
Trial Completion Date		2008-10-31 (estimated)
Registered in ClinicalTrials.gov		NCT00079053
Date Submitted to PDQ		2004-01-20
Information Last Verified		2008-05-20

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