RATIONALE: Erlotinib 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. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with radiation therapy with or without cisplatin may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with radiation therapy with or without cisplatin in treating patients who have advanced mouth or throat cancer.

Condition	Treatment or Intervention	Phase
stage II squamous cell carcinoma of the lip and oral cavity stage II squamous cell carcinoma of the oropharynx stage III squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the lip and oral cavity stage IV squamous cell carcinoma of the oropharynx	Drug: cisplatin  Drug: erlotinib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib administered with radiotherapy with or without cisplatin in patients with stage II, III, or IV squamous cell carcinoma of the oral cavity or oropharynx.
• Determine the safety of these regimens in these patients.
• Determine biological markers of activity of erlotinib in tumor biopsy specimens from these patients before and after treatment with these regimens.
• Determine the ability of fludeoxyglucose F 18 positron-emission tomography scan to demonstrate biological activity of erlotinib and predict clinical response in patients treated with these regimens.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to 1 of 2 regimens according to disease stage.

• Regimen A (patients with stage II [T2, N0] or III [T1-2, N1] disease): Patients receive oral erlotinib once daily. Beginning on day 15, patients also undergo radiotherapy once daily 5 days a week for 7 weeks.
• Regimen B (patients with stage III [T3, N0-1] or IV [T1-4, N2-3, M0 or T4, N0-1, M0] disease): Patients receive oral erlotinib and radiotherapy as in regimen A. Patients also receive cisplatin IV over 20 minutes on each day of radiotherapy. Patients in both regimens continue to receive erlotinib until the last day of radiotherapy (patients already in the maintenance phase of this study as of 5/11/04 continue to receive erlotinib once daily for up to 2 years) in the absence of disease progression or unacceptable toxicity.

In both regimens, cohorts of 3-6 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 30 days and then every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 24-48 patients (12-24 per regimen) will be accrued for this study within 6-24 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP)
• OC sites include: oral tongue, buccal mucosa, floor of mouth, retromolar trigone, alveolar ridge, hard palate, and mucosal lip
• OP sites include: base of tongue, tonsil, soft palate, and oropharyngeal wall
• Stage II (T2, N0) or III (T1-2, N1) (eligible for regimen A only)
• Stage III (T3, N0-1) or IV (T1-4, N2-3, M0 or T4, N0-1, M0) (eligible for regimen B only)
• Documentation of evaluable tumor within the past 4 weeks
• Operable or inoperable tumors allowed
• No known brain involvement
• No prior head and neck malignancies

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin normal (unless due to hemolysis or Gilbert's syndrome)
• AST/ALT no greater than 2.5 times upper limit of normal
• aPTT/INR normal (correctable with vitamin K)

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No untreated or new cardiac arrhythmia

Ophthalmic

• No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital abnormalities (e.g., Fuch's dystrophy)
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Gastrointestinal

• G-tube dependency allowed
• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• No active peptic ulcer disease
• No known malabsorption syndrome

Other

• No other concurrent uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No uncontrolled diabetes mellitus
• No psychiatric illness or social situation that would preclude study participation
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or other study agents
• No significant traumatic injury within the past 28 days
• No other malignancy within the past 3 years except completely resected basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for this malignancy

Chemotherapy

• No prior chemotherapy for this malignancy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this malignancy

Surgery

• No prior surgical procedures affecting absorption
• At least 28 days since prior major surgery

Other

• No prior epidermal growth factor receptor-targeting therapies for this malignancy
• No prior investigational agents for this malignancy
• No other prior therapy for this malignancy
• No concurrent commercial or other investigational anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent warfarin

Louisiana
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      New Orleans Cancer Institute At Memorial Medical Center, New Orleans,  Louisiana,  70115,  United States; Recruiting
      Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting

Study chairs or principal investigators

Maura Gillison, MD, PhD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000257942; JHOC-20020723; NCI-5375; NCT00049166
Record last reviewed:  July 2004
Last Updated:  March 3, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049166
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08