Dasatinib in Treating Patients With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well dasatinib works in treating patients with metastatic pancreatic cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the overall survival, including median survival, of patients with metastatic adenocarcinoma of the pancreas treated with dasatinib. SECONDARY OBJECTIVES: I. Determine the effects of this drug on quantities of circulating tumor cells in these patients. II. Determine the time to progression in patients treated with this drug. III. Determine pre- and post-drug fat-free mass and gait speed in patients treated with this drug. IV. Evaluate the toxicity of this drug in these patients. V. Evaluate objective response rate in patients treated with this drug. OUTLINE: This is an open-label, multicenter study. Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection at baseline and during days 25-31. Samples are analyzed for quantification of circulating tumor cells. Patients also undergo analysis of fat-free mass and gait speed at baseline and at 1, 2, and 6 months. After completion of study treatment, patients are followed periodically.

Official Title
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Phase II Study of Dasatinib (BMS-354825) in Patients With Metastatic Adenocarcinoma of the Pancreas

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: dasatinib
* Procedure: laboratory biomarker analysis
* Procedure: physiologic testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the pancreas Metastatic disease Measurable or evaluable/nonmeasurable disease No known brain metastases ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% Life expectancy > 12 weeks Absolute granulocyte count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin > 8.5 g/dL Bilirubin =< 1.5 times upper limit of normal (ULN) AST and ALT =< 2.5 times ULN Creatinine =< 2.0 mg/dL Not pregnant or nursing No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib No QTc prolongation (i.e., QTc interval >= 480 msecs [Fridericia correction]) or other significant ECG abnormalities LVEF normal by MUGA scan No condition that impairs ability to swallow and retain dasatinib tablets, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation Prior surgical procedures affecting absorption Active peptic ulcer disease No clinically significant cardiovascular disease, including any of the following: Myocardial infarction or ventricular tachyarrhythmia within the past 6 months Major conduction abnormality (unless a cardiac pacemaker is present) Recovered from all prior therapy More than 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or mitomycin C) and/or radiotherapy No prior chemotherapy for metastatic disease More than 4 weeks since prior EGFR inhibitors (e.g., imatinib mesylate, gefitinib, erlotinib hydrochloride, or lapatinib ditosylate) No prior EGFR inhibitors that target Src kinases At least 7 days since prior and no concurrent agents with proarrhythmic potential No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent grapefruit or grapefruit juice No other concurrent anticancer agents or therapies No concurrent systemic antacids (i.e., H2-receptor antagonists and proton pump inhibitors) [Locally acting antacids (e.g., Maalox, Mylanta) allowed within either 2 hours before or 2 hours after dasatinib therapy] No concurrent uncontrolled illness, including, but not limited to, any of the following: Ongoing or active infection History of significant bleeding disorder, including congenital (von Willebrand's disease) or acquired (anti-factor VIII antibodies) disorders Large pleural effusions Psychiatric illness or social situation that would preclude study compliance More than 7 days since prior and no concurrent CYP3A4 inducers or inhibitors No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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: Dasatinib Treatment<br>Patients receive oral dasatinib twice daily on days 1-28. | Drug: dasatinib<br> <br> * Other names: Sprycel;Procedure: laboratory biomarker analysis<br>* Correlative study<br>Procedure: physiologic testing<br>* Correlative study<br>* Other names: study of physiologic variables;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | From the date of onset of treatment to the date of death and to the date of last follow-up for those still alive, assessed up to 24 months | assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (Complete Response, Partial Response, or Stable Disease), Evaluated Using the New International Criteria Proposed by the RECIST Committee | Response is defined as CR (Complete Response), PR (Partial Response) or SD (Stable Disease) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. SD: neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease (PD). Progressive disease (PD) is defined as: at least a 20% increase in the sum of the LD of target lesions. | Up to 5 years | 
| Median Progression Free Survival (PFS) | Number of months patients were free of disease progression, defined as < 20% increase in the sum of the LD of target lesions nor the appearance of one or more new lesions. | Up to 5 years | 
| Gait Speed | Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch. | baseline | 
| Gait Speed | Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch. | at 8 weeks |