Dasatinib in Treating Patients With Stage IV Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00544908
• Other study ID #: 07024
• Secondary ID: P30CA033572CHNMC
• Status: Terminated
• Phase: Phase 2
• First received: October 13, 2007
• Last updated: September 18, 2015
• Start date: September 2007

Study information

• Verified date: September 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• dasatinib

Other:
• immunoenzyme technique

• immunohistochemistry staining method

• laboratory biomarker analysis

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No