OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib in combination with gemcitabine in patients with recently diagnosed, gemcitabine-naive, locally advanced or metastatic pancreatic carcinoma or other potentially responsive solid tumor.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the objective antitumor response rate and response duration in patients treated with this regimen.
• Determine the time to disease progression and duration of overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib.

Patients receive gemcitabine IV over 30 minutes on day 1 of weeks 1-7 and oral erlotinib once daily beginning on day 3 of week 1 and continuing for 8 weeks (course 1). Patients receive subsequent courses of therapy comprising gemcitabine once weekly for 3 weeks and erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are accrued and treated at the MTD as above.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 3 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced or metastatic epithelial carcinoma of the pancreas or other malignancy considered to be potentially responsive to gemcitabine

  • Newly diagnosed or gemcitabine naive
• Measurable or evaluable disease
• Not amenable to surgical intervention due to medical contraindications or non-resectability of the tumor
• No islet cell tumors or other non-epithelial cell carcinomas of the pancreas

• No active CNS metastases or leptomeningeal disease

  • Treated or asymptomatic brain metastases are allowed if on a stable dose of corticosteroids and/or there is no change in brain disease status for at least 4 weeks after related therapy (e.g., whole-brain radiotherapy)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 2.0 mg/dL (except for documented Gilbert's syndrome)
• AST or ALT less than 2 times upper limit of normal (ULN) (no greater than 5 times ULN if hepatic obstruction or metastases present)
• Albumin at least 2.5 g/dL

Renal:

• Creatinine less than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No significant cardiovascular disease
• No history of congestive heart failure currently requiring therapy
• No ventricular arrhythmia requiring anti-arrhythmic therapy
• No severe conduction disturbances
• No angina pectoris requiring therapy
• No myocardial infarction within the past 6 months

Gastrointestinal:

• No significant gastrointestinal abnormalities including:

  • Requirement for IV alimentation
  • Active peptic ulcer disease

Ophthalmic:

• No significant ophthalmologic abnormalities including:

  • Severe dry eye syndrome
  • Keratoconjunctivitis sicca
  • Sjogren's syndrome
  • Severe exposure keratopathy
  • Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
  • Abnormal Schirmer test (less than 2 mm) allowed provided there is no evidence of clinically significant corneal surface abnormalities

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known or suspected hypersensitivity to gemcitabine
• No uncontrolled infection
• HIV negative
• No other malignancy within the past 5 years except treated non-melanoma skin cancer or carcinoma in situ of the breast or cervix
• No other life-threatening illness
• No psychiatric disorders or altered mental status the would preclude informed consent or study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 28 days since prior immunotherapy or biological response modified therapy for the primary malignancy
• No concurrent immunotherapy or biologic response modifier therapy for the primary malignancy

Chemotherapy:

• See Disease Characteristics
• At least 28 days since prior chemotherapy for the primary malignancy
• No prior mitomycin or nitrosoureas for the primary malignancy
• No more than 6 prior courses of chemotherapy with an alkylating agent for the primary malignancy
• No prior gemcitabine for the primary malignancy except as a low-dose (less than 500 mg/m^2) radiosensitizer administered concurrently with or within 2 weeks after radiotherapy at least 3 months ago
• No other concurrent chemotherapy for the primary malignancy

Endocrine therapy:

• See Disease Characteristics
• At least 28 days since prior systemic hormonal therapy (except LH-RH agonists) for the primary malignancy
• No concurrent systemic hormonal therapy (except LH-RH agonists) for the primary malignancy

• Other concurrent endocrine therapy is allowed as follows:

  • Hormonal therapy (e.g., megestrol) for appetite stimulation
  • Nasal, ophthalmic, or topical glucocorticoids
  • Oral glucocorticoids for adrenal insufficiency
  • Low-dose maintenance steroids

Radiotherapy:

• See Disease Characteristics
• At least 28 days since prior radiotherapy for the primary malignancy or metastases and recovered
• No prior wide-field radiotherapy to 25% or more of marrow-bearing bone
• No prior pelvic irradiation
• No concurrent radiotherapy for the primary malignancy or metastases
• No concurrent wide-field radiotherapy for pain management

Surgery:

• See Disease Characteristics
• Recovered from any prior surgery
• No prior surgical procedures affecting absorption

Other:

• No prior agent for the primary malignancy targeting the epidermal growth factor receptor (EGFR) or EGFR-specific tyrosine kinase activity