Dasatinib in Treating Patients With Stage IV Pancreatic Cancer

City of Hope

Status and phase

Terminated

Phase 2

Conditions

Pancreatic Cancer

Treatments

Drug: dasatinib

Other: laboratory biomarker analysis

Procedure: quality-of-life assessment

Other: immunoenzyme technique

Other: immunohistochemistry staining method

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00544908

CHNMC-07024

P30CA033572 (U.S. NIH Grant/Contract)

CDR0000570288 (Registry Identifier)

07024

BMS-CA180-114

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)