RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase I/II trial to study the effectiveness of erlotinib in treating patients who have metastatic or unresectable non-small cell lung cancer, ovarian cancer, or squamous cell carcinoma (cancer) of the head and neck.

Condition	Treatment or Intervention	Phase
Drug Toxicity female reproductive cancer Head and Neck Cancer thorax and respiratory cancer	Drug: erlotinib  Procedure: complications of therapy assessment/management  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: supportive care/therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Correlate the length of the CA dinucleotide repeat polymorphism in the epidermal growth factor receptor (EGFR) gene with observed toxicity in patients with advanced non-small cell lung cancer, ovarian cancer, or squamous cell carcinoma of the head and neck treated with erlotinib.
• Determine the pharmacodynamic effects of this drug on EGFR activity and MAP kinase signaling in these patients.
• Correlate toxicity and inhibition of EGFR phosphorylation with the area under the curve in patients treated with this drug.
• Determine the observed antitumor response in patients treated with this drug.
• Determine the toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to length of CA dinucleotide repeat polymorphism (short vs medium vs long).

Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 20 months.

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

Criteria

DISEASE CHARACTERISTICS:

• One of the following histologically or cytologically confirmed malignancies:
• Non-small cell lung cancer
• Ovarian cancer
• Squamous cell carcinoma of the head and neck
• Metastatic or unresectable disease
• Measurable or evaluable disease
• No uncontrolled brain metastases
• Previously treated brain metastases allowed provided neurologic status has been stable for at least 4 weeks after therapy and there is no neurologic dysfunction that would confound evaluation of adverse events

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

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

Renal

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

Cardiovascular

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

Ophthalmic

• No significant ophthalmologic abnormalities*, including any of the following:
• Severe dry eye syndrome
• Keratoconjunctivitis sicca
• Sjögren's syndrome
• Severe exposure keratopathy
• Disorders that increase the risk for epithelium-related complications, including any of the following:
• Bullous keratopathy
• Aniridia
• Severe chemical burns
• Neutrophilic keratitis NOTE: *Patients with mild forms of the listed conditions, an asymptomatic history, or normal ophthalmologic exam may be eligible at the discretion of the investigator

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to erlotinib
• No significant traumatic injury within the past 14 days
• No other uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No serious nonhealing wound ulcer or bone fracture

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 4 weeks since prior biologic therapy

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 14 days since prior major surgery or open biopsy

Other

• Recovered from all prior therapy
• At least 4 weeks since other prior investigational therapy
• No prior small molecule epidermal growth factor receptor inhibitors, including erlotinib and gefitinib
• No other concurrent therapy for the malignancy
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting

Study chairs or principal investigators

Charles M. Rudin, MD, PhD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000304628; JHOC-J0384; UCCRC-12202A; NCI-5948; NCT00063895
Record last reviewed:  May 2004
Last Updated:  December 6, 2004
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00063895
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08