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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as erlotinib use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy and biological therapy may kill more tumor cells. It is not yet known if gemcitabine is more effective with or without erlotinib in treating pancreatic cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of gemcitabine with and without erlotinib in treating patients who have unresectable locally advanced or metastatic pancreatic cancer.

Detailed Description
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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.

Official Title
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A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OSI-774 plus Gemcitabine<br> | Drug: erlotinib hydrochloride<br>* 150 mg po daily<br>Drug: gemcitabine hydrochloride<br>* 1000 mg/m2 IV weekly (Cycle 1 -Day 1, 8, 15, 22, 29, 36, 43 of an 8 week cycle, Cycle 2 and subsequent cycles -Day 1,8 and 15 of a 4 week cycle)<br>|
| Active Comparator: Placebo plus gemcitabine<br> | Drug: gemcitabine hydrochloride<br>* 1000 mg/m2 IV weekly (Cycle 1 -Day 1, 8, 15, 22, 29, 36, 43 of an 8 week cycle, Cycle 2 and subsequent cycles -Day 1,8 and 15 of a 4 week cycle)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 3 years | 
| Quality of Life | Canada, US and selected countries only | 3 years | 
| Response rates | Complete and partial response only. | 3 years | 
| Toxicity |  | 3 years | 
| EGFR levels | Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment | 3 years | 
| Pharmacokinetics | To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III pancreatic cancer, adenocarcinoma of the pancreas, stage IV pancreatic cancer