A Phase I/Expansion Study of Dasatinib

• Status: Terminated
• Trial end date: 2012-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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 will try to find 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: Bristol-Myers Squibb
• Treatments: Dasatinib; Gemcitabine

Criteria

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.