Gefitinib and Docetaxel in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose of gefitinib when administered with docetaxel in patients with advanced solid tumors.
• Determine the safety and efficacy of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gefitinib.

Patients receive oral gefitinib once daily on days 1 and 2 and docetaxel IV over 1 hour on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor
• Failed standard treatment OR no standard treatment exists
• Measurable or evaluable indicator lesions
• No uncontrolled CNS metastases (i.e., any known CNS lesion that is progressive [e.g., ≥ 25% growth], symptomatic, and/or requires escalating doses of corticosteroids)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2.0 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 55 mL/min

Cardiovascular

• No congestive heart failure
• No recent myocardial infarction
• No unstable angina
• No uncontrolled hypertension

Pulmonary

• No clinically active interstitial lung disease

• Chronic, stable, asymptomatic radiographic changes allowed

Ophthalmic

• No corneal abnormality
• No history of dry eye syndrome or ocular surface diseases

Other

• No known severe hypersensitivity to gefitinib or any of its excipients
• No unstable systemic disease
• No active infection
• No other significant medical history or unstable medical condition
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No sperm donation during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 3 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for metastatic cancer
• No prior docetaxel

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• At least 3 weeks since prior radiotherapy to a major bone marrow-containing area

Surgery

• Not specified

Other

• No prior gefitinib or erlotinib
• No other prior epidermal growth factor receptor tyrosine kinase inhibitors
• More than 30 days since prior non-approved or other investigational drugs
• No concurrent administration of any of the following CYP3A4 inhibitors or inducers:

• Ketoconazole
• Itraconazole
• Clarithromycin
• Erythromycin
• Grapefruit juice
• Troleandomycin
• Diltiazem
• Verapamil
• Rifampin
• Phenytoin
• Carbamazepine
• Barbiturates
• Hypericum perforatum (St. John's wort)
• No concurrent warfarin
• No concurrent drugs that cause significant sustained elevations of gastric pH (pH ≥ 5)