The purpose of this study is to find the highest dose of the drugs gemcitabine and dasatinib that can be given for the treatment of pancreatic cancer.

Gemcitabine (also called Gemzar™)is a drug that is given intravenously. Dasatinib (also called Sprycel™) is a tablet and will be taken by mouth.

Gemcitabine is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast, lung, and pancreatic cancer. Dasatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia, or for patients that are resistant to imatinib mesylate (Gleevec™).

This study is trying to determine the highest doses of these drugs that can be tolerated when taken in combination. The study will also look at how the drugs work in the body, and will see if there is any effect on pancreatic cancer.

Eligibility

To participate in this study, patients must be 18 years of age or older and have:

• Karnofsky performance status greater than 70 percent 
• Life expectancy of at least three months
• Ability to understand and the willingness to sign a written informed consent document
• Met lab requirements as defined in the protocol 
• Ability to take oral medications for prolonged compliance
• An effective method of birth control if you are a sexually active woman of child-bearing potential
• A negative pregnancy test (if applicable) within seven days prior to first receiving the investigational products

Eligibility Criteria Specific for Dose Escalation Phase

For the dose escalation phase, patients must have:

• Histologically confirmed solid tumor malignancy that is metastatic or unresectable to standard treatment including gemcitabine or for which standard curative or palliative measures do not exist or are no longer effective
• Not had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day

Eligibly Criteria Specific for Expansion Phase at Recommended Phase II Dose

For phase two of the dose escalation phase, patients must have:

• Histologically or cytologically documented adenocarcinoma of the pancreas
• Metastatic pancreatic cancer as documented by radiologic study or surgical evidence of metastatic disease
• No prior chemotherapy for metastatic pancreatic disease. Patients may have received a radiosensiting dose of 5-fluorouracil or capecitabine or other agents used as radiosensitizers with concurrent radiation therapy.
• Taken the last dose of adjuvant chemotherapy at least four weeks prior to the first day of the study drug treatment 
• Received no prior treatment with gemcitabine or dasatinib in the adjuvant or metastatic setting but prior gemcitabine use is allowed if the gemcitabine was administered in the adjuvant setting and more than six months has elapsed between diagnosis of metastatic disease and last gemcitabine treatment
• No history for other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with a current PSA of <1.0 mg/dL on two successive evaluations, at least three months apart, with the most recent evaluation no more than four weeks prior to the first day of the study drug treatment 

Prior radiation therapy is allowed prior to the first day of the study drug treatment. At least four weeks must have elapsed to baseline or grade one.

Pregnant and/or lactating women will be excluded from this study. 

Exclusion Criteria

Patients will be exluded from the trial if they have:

• Had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within 28 days prior to day one of the study drug treatment. Patients receiving hormonal therapy for metastatic prostate or breast cancer may continue hormonal therapy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first day of the study drug treatment 
• Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device within seven days prior to the expected start of the treatment
• Received any other investigational agents within the 28 days prior to day one of the study drug treatment
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within six months prior to day one of the study drug treatment
• History of stroke or transient ischemic attack within six months prior to day of the study drug treatment
• Uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class II or greater 
• Known cardiomyopathy with decreased ejection fraction (less than institutional normal limits) 
• Diagnosed or congenital long QT syndrome 
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) 
• Prolonged QTc interval on pre-study electrocardiogram (> 450 msec) 
• History of significant bleeding episodes (for example, hemoptysis, upper or lower GI bleeding) within the previous six months of day one of the study drug treatment 
• Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least two weeks prior to day one of the study drug treatment
• History of significant bleeding disorder unrelated to cancer 
• Medications that inhibit platelet function
• Fluid retention (i.e. pleural effusion, ascites, edema) grade is greater than two
• History of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment
• Currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes 
• Actively taking inhibitors or inducers of CYP3A4
• Actively taking proton pump inhibitors or H2 antagonists
• Other concurrent severe and/or poorly controlled medical condition that could compromise safety of treatment
• Any psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results

For more information, contact the clinical research coordinator at 919-668-1861.