Clinical trial NCT00544908: Dasatinib in Treating Patients With Stage IV Pancreatic Cancer
Official title: A Phase II Clinical Trial of Dasatinib in Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: stage IV pancreatic cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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)

Primary outcomes:
measure: Progression-free Survival (PFS) Rate at 4 Months
timeFrame: Four months.
Secondary outcomes:
measure: Response Rate
timeFrame: After every two cycles, up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: City of Hope Medical Group
state: California
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Vincent Chung, MD
role: PRINCIPAL_INVESTIGATOR
References: