A Phase I Study of the Combination of Gemcitabine Plus Dasatinib in Patients With Refractory Solid Tumors With an Expanded Cohort in Advanced Pancreatic Cancer

Inclusion Criteria:

Eligibility Criteria Specific for Dose Escalation Phase

- Patients must have histologically confirmed solid tumor malignancy that is metastatic
or unresectable and for which standard therapy would include gemcitabine or for which
standard curative or palliative measures do not exist or are no longer effective.

- Patients must not have had radiation therapy, hormonal therapy, biologic therapy or
chemotherapy for cancer within the 28 days prior to study day 1.

Eligibly Criteria Specific for Expansion Phase at Recommended Phase II Dose

- 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.

- Last dose of adjuvant chemotherapy must be at least 4 weeks prior to day 1 of the
study drug treatment

- Prior radiation therapy is allowed. prior to day 1 of the study drug treatment. At
least 4 weeks must have elapsed to baseline or grade 1.

- No prior treatment with gemcitabine or dasatinib in the adjuvant or metastatic
setting.

- Prior gemcitabine only allowed if the gemcitabine was administered in the adjuvant
setting and > 6 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 2 successive evaluations, at least 3 months
apart, with the most recent evaluation no more than 4 weeks prior to day 1 of the
study drug treatment. .

Eligibility Criteria for All Subjects

- Age >18 years.

- Karnofsky performance status >70%.

- Life expectancy of at least 3 months.

- Ability to understand and the willingness to sign a written informed consent
document.

- Must meet lab requirements as defined in the protocol

- Patients should be capable of taking oral medications for prolonged compliance.

- Sexually active women of childbearing potential must use an effective method of birth
control.

- All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving
investigational product.

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

Exclusion Criteria:

- Patients who have had radiation therapy, hormonal therapy, biologic therapy, or
chemotherapy for cancer within 28 days prior to day 1 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 day 1 of the study drug treatment

- Core biopsy or other minor surgical procedure excluding study-related procedures or
placement of a vascular access device within 7 days prior to expected start of
treatment.

- Patients who have received any other investigational agents within the 28 days prior
to day 1 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 6 months prior to day 1 of the study drug
treatment.

- History of stroke or transient ischemic attack within 6 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)

- Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or
lower GI bleeding) within the previous 6 months of day 1 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 2 weeks prior to day 1 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 > 2.

- A known history of HIV seropositivity, hepatitis C virus, acute or chronic active
hepatitis B infection, or other serious chronic infection requiring ongoing
treatment.

- Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes

- Patients actively taking inhibitors or inducers of CYP3A4

- Patients 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.

- Patients unwilling to or unable to comply with the protocol.