Gemcitabine With/Out Erlotinib in Unresectable Locally Advanced/Metastatic Pancreatic Cancer

OBJECTIVES:

• Compare the overall survival rate in patients with unresectable locally advanced or metastatic pancreatic cancer treated with gemcitabine with or without erlotinib.
• Compare the progression-free survival rate in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the response rate and response duration in patients treated with these regimens.
• Compare the nature, severity, and frequency of toxic effects of these regimens in these patients.
• Correlate the expression of tissue epidermal growth factor receptor levels at diagnosis with outcome and response in patients treated with these regimens.
• Determine the pharmacokinetics of erlotinib in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, extent of disease (locally advanced vs metastatic), and ECOG performance status (0-1 vs 2). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 of course 1 only, which lasts 8 weeks, and on days 1, 8, and 15 of all subsequent courses, which last 4 weeks each. Patients also receive 1 of 2 doses of oral erlotinib once daily.
• Arm II: Patients receive gemcitabine as in arm I and 1 of 2 doses of oral placebo once daily.

Treatment continues in both arms in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 29 of course 1, on day 1 of all subsequent courses, at 4 weeks after study, and then every 12 weeks until disease progression.

Patients are followed at 4 weeks and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 800 patients (400 per treatment arm) will be accrued for this study within 11 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Locally advanced or metastatic disease that is considered unresectable
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• AST and/or ALT less than 2 times ULN (5 times ULN if liver metastases present)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No uncontrolled high blood pressure
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication

Gastrointestinal:

• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication such as uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No post-surgical malabsorption characterized by:

• Uncontrolled diarrhea that results in weight loss and vitamin deficiency OR
• Requires IV hyperalimentation
• Pancreatic enzyme supplementation allowed provided that the above criteria are not met

Ophthalmic:

• No ocular inflammation or infection unless fully treated prior to study
• No significant ophthalmologic abnormalities, including the following:

• Severe dry eye syndrome
• Sjogren's syndrome
• Keratoconjunctivitis sicca
• Severe exposure keratopathy
• Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No serious active infection
• No other serious underlying medical, psychological, or geographical condition that would preclude study participation
• No prior allergic reaction to compounds with similar chemical or biologic composition to erlotinib
• No other prior malignancy within the past 5 years except cancer in situ or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy or immunotherapy

Chemotherapy:

• No prior chemotherapy except fluorouracil (with or without leucovorin calcium) or gemcitabine administered concurrently with radiotherapy as a radiosensitizer
• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Chemotherapy
• At least 4 weeks since prior radiotherapy and recovered
• Prior radiotherapy for local disease allowed if evidence of disease progression has occurred
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 2 weeks since prior major surgery
• No concurrent ophthalmic surgery

Other:

• No prior epidermal growth factor receptor inhibitors
• At least 2 weeks since prior investigational drug
• No other concurrent investigational drugs during and for at least 30 days after study
• No other concurrent anti-cancer therapy