Erlotinib in Treating Patients With Stage III or Stage IV Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with stage III or stage IV pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the progression-free survival (PFS) of patients with stage III or IV adenocarcinoma of the pancreas treated with erlotinib hydrochloride as first- or second-line therapy. Secondary Determine the proportion of patients with a radiological response to this drug. Determine the overall survival of these patients. Determine the effect of this drug on quality of life in these patients. Correlate expression of EGFR, E-cadherin, P-cadherin, vimentin, cytokeratin, fibronectin, and ki67 in baseline tumor blocks and presence of K-ras mutations in baseline tumor biopsy specimens with response to this drug. Correlate smoking status with PFS in patients treated with this drug. Collect serum samples before, during, and after therapy for future serum proteomic studies and for development of profiles of responders to this drug. OUTLINE: Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients complete a questionnaire about their smoking status at baseline. Patients also complete questionnaires about their quality of life every three weeks during study therapy and after completion of study therapy. Blood samples are collected from patients at baseline and periodically during study for future serum proteomic research and for development of profiles of responders to erlotinib hydrochloride therapy. Paraffin-embedded tumor tissue from diagnostic tumor biopsies is assessed at baseline for expression of EGFR, E-cadherin, P-cadherin, vimentin, cytokeratin, fibronectin, and ki67 by immunohistochemical analysis. Tissue from surgical specimens in patients with prior resection is assessed for K-ras mutations by K-ras analysis. After completion of study therapy, patients are followed for at least 6 months. PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Official Title
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Phase II Study of Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas Locally advanced inoperable or metastatic disease (stage III or IV disease) No more than 1 prior systemic therapy Patients who have not received 1 prior systemic therapy must meet 1 of the following criteria: Ineligible for or refused chemoradiotherapy AND has stage III disease Ineligible for or refused gemcitabine hydrochloride-based chemotherapy AND has stage IV disease No brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 3 months WBC > 3,000/mm³ ANC > 1,500/mm³ Platelet count > 100,000/mm³ Bilirubin ≤ 2 mg/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in patients with documented liver metastases) Creatinine < 1.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study therapy No uncontrolled comorbid illness that is likely to increase toxicity of the study drug or to interfere with toxicity evaluation No known allergy to the study drug or its excipients No symptomatic interstitial pulmonary disease PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior adjuvant therapy allowed provided it was completed at least 28 days prior to study entry No prior EGFR-inhibitor No concurrent drugs that are known to be strong inducers or inhibitors of the CYP450 enzyme system No concurrent Hypericum perforatum (St. John's wort) No concurrent investigational or commercial agents or therapies with the intent to treat the patient's malignancy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - Oral Erlotinib hydrochloride<br>Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity | Drug: erlotinib hydrochloride<br>* Oral<br>Other: immunohistochemistry staining method<br>* Correlative Study<br>Other: laboratory biomarker analysis<br>* Correlative Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion | Every cycle for up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response (Complete and Partial Response) as Measured by RECIST Criteria |  | After every cycle | 
| Median Overall Survival |  | After every cycle | 
| Change in Quality of Life (QOL) as Measured by EORTC PAN26 Every 3 Weeks During Study Therapy and After Completion of Study Therapy |  | Every 3 weeks | 
| Correlation of Smoking Status With Overall Survival |  | Every 3 weeks | 
| Correlation of Response, QOL, and Survival With EGFR, E-cadherin, P-cadherin, Vimentin, Cytokeratin, ki67, and Fibronectin and With Other Prognostic Variables, Such as Age and Tumor Grade |  | At Baseline | 

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