Dasatinib in Treating Patients With Stage IV Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Dasatinib 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 dasatinib works in treating patients with stage IV pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate the 4-month progression-free survival (PFS) rate in patients with stage IV pancreatic cancer treated with dasatinib. Secondary To evaluate the response rate (complete and partial response) in patients treated with this drug. To evaluate the median PFS and overall survival of patients treated with this drug. To study the toxicities and tolerability of this drug in these patients. To evaluate the impact of this drug on quality of life measures. To evaluate the impact of this drug on Src and FAK in peripheral blood mononuclear cells prior to and during treatment. To study the pre-treatment expression of various signaling molecules in the Src and STAT3 pathways and attempt to identify a relationship between these findings and the aggressiveness of the tumor or its response to treatment with dasatinib. OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection periodically for correlative and biological studies. Blood samples are analyzed for phosphorylation levels of proteins, including phospho-Src, phospho-Fak, and other relevant biomarkers, by western blotting. Tumor tissue samples are analyzed for biomarkers by immunohistochemistry. Quality of life is assessed at baseline, after every other course during treatment, and then at 1 year after treatment using the FACT-HEP questionnaire. After completion of study treatment, patients are followed every 2 months.

Official Title
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A Phase II Clinical Trial of Dasatinib in Patients With Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: dasatinib
* Other: immunoenzyme technique
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* confirmed pancreatic cancer Stage IV disease NOTE: *If biopsy was performed at an outside facility, the histology must be reviewed and confirmed by the Division of Pathology at the City of Hope PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy ≥ 3 months Platelet count ≥ 100,000/μL Absolute neutrophil count ≥ 1,500/μL Bilirubin ≤ 1.5 mg/dL ALT and AST ≤ 2.5 times upper limit of normal (ULN) Creatinine ≤ 1.5 mg/dL and/or creatinine clearance > 60 mL/min PT and PTT ≤ 1.5 times ULN Able to swallow dasatinib whole No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix, uterus, or bladder No concurrent medical condition which may increase the risk of toxicity, including any of the following: Pleural or pericardial effusion of any grade Clinically significant coagulation or platelet function disorder (e.g., known von Willebrand's disease) None of the following cardiac conditions: Uncontrolled angina, congestive heart failure, or myocardial infarction within the past 6 months Prolonged QTc interval (i.e., QTc > 450 msec) on electrocardiogram History of clinically significant ventricular arrhythmias (i.e., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) No hypokalemia or hypomagnesemia that cannot be corrected No severe infection requiring treatment Completely recovered from other concurrent illnesses, as deemed by the investigator Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Recovered from prior major surgery No prior irradiation to the planned field No prior chemotherapy for pancreatic cancer At least 7 days since prior and no concurrent medications that may prolong the QT interval, including any of the following: Quinidine Procainamide Disopyramide Amiodarone Sotalol Ibutilide Dofetilide Erythromycin Clarithromycin Chlorpromazine Haloperidol Mesoridazine Thioridazine Pimozide Cisapride Bepridil Droperidol Methadone Arsenic Chloroquine Domperidone Halofantrine Levomethadyl Pentamidine Sparfloxacin Lidoflazine At least 7 days since prior and no concurrent potent CYP3A4 inhibitors At least 7 days since prior and no concurrent medications that directly and durably inhibit platelet function, including any of the following: Aspirin or aspirin-containing combinations Clopidogrel Dipyridamole Tirofiban Dipyridamole Epoprostenol Eptifibatide Cilostazol Abciximab Ticlopidine Cilostazol No concurrent anticoagulants, including warfarin or heparin/low molecular weight heparin (e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin) Low-dose warfarin for prophylaxis to prevent catheter thrombosis or heparin for flushes of IV lines allowed No concurrent IV bisphosphonates during the first 8 weeks of dasatinib therapy No concurrent Hypericum perforatum (St. Johns wort)

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<br>Dasatinib 70 mg po bid (1 cycle=28 days) | Drug: dasatinib<br> <br> Other: immunoenzyme technique<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Rate at 4 Months | Progressive disease - appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the treating physician should prevail and the progression status should be confirmed later on by a review panel (or study chair/primary investigator). | Four months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | After every two cycles, up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV pancreatic cancer