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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00079053

Collaborator

Roche Pharma AG (Industry)

Enrollment

Locations

86.4

Actual Duration (Months)

9.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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: This phase I trial is studying the side effects and best dose of adjuvant erlotinib when given after completing chemoradiotherapy in treating patients with locally advanced squamous cell carcinoma (cancer) of the head and neck.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: erlotinib hydrochloride Procedure: adjuvant therapy	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 5, 2003

Actual Primary Completion Date :

Dec 9, 2008

Actual Study Completion Date :

Jan 18, 2011

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)