Clinical trial NCT00474812: Dasatinib in Treating Patients With Metastatic Pancreatic Cancer
Official title: Phase II Study of Dasatinib (BMS-354825) in Patients With Metastatic Adenocarcinoma of the Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-05-17
Enrollment: 51
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: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well dasatinib works in treating patients with metastatic pancreatic cancer.

Detailed description: PRIMARY OBJECTIVE:

I. Determine the overall survival, including median survival, of patients with metastatic adenocarcinoma of the pancreas treated with dasatinib.

SECONDARY OBJECTIVES:

I. Determine the effects of this drug on quantities of circulating tumor cells in these patients.

II. Determine the time to progression in patients treated with this drug. III. Determine pre- and post-drug fat-free mass and gait speed in patients treated with this drug.

IV. Evaluate the toxicity of this drug in these patients. V. Evaluate objective response rate in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and during days 25-31. Samples are analyzed for quantification of circulating tumor cells. Patients also undergo analysis of fat-free mass and gait speed at baseline and at 1, 2, and 6 months.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas
* Metastatic disease
* Measurable or evaluable/nonmeasurable disease
* No known brain metastases
* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* Life expectancy \> 12 weeks
* Absolute granulocyte count \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \> 8.5 g/dL
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* AST and ALT =\< 2.5 times ULN
* Creatinine =\< 2.0 mg/dL
* Not pregnant or nursing
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib
* No QTc prolongation (i.e., QTc interval \>= 480 msecs \[Fridericia correction\]) or other significant ECG abnormalities
* LVEF normal by MUGA scan
* No condition that impairs ability to swallow and retain dasatinib tablets, including any of the following:

  * Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  * Prior surgical procedures affecting absorption
  * Active peptic ulcer disease
* No clinically significant cardiovascular disease, including any of the following:

  * Myocardial infarction or ventricular tachyarrhythmia within the past 6 months
  * Major conduction abnormality (unless a cardiac pacemaker is present)
* Recovered from all prior therapy
* More than 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or mitomycin C) and/or radiotherapy
* No prior chemotherapy for metastatic disease
* More than 4 weeks since prior EGFR inhibitors (e.g., imatinib mesylate, gefitinib, erlotinib hydrochloride, or lapatinib ditosylate)
* No prior EGFR inhibitors that target Src kinases
* At least 7 days since prior and no concurrent agents with proarrhythmic potential
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent grapefruit or grapefruit juice
* No other concurrent anticancer agents or therapies
* No concurrent systemic antacids (i.e., H2-receptor antagonists and proton pump inhibitors) \[Locally acting antacids (e.g., Maalox, Mylanta) allowed within either 2 hours before or 2 hours after dasatinib therapy\]
* No concurrent uncontrolled illness, including, but not limited to, any of the following:

  * Ongoing or active infection
  * History of significant bleeding disorder, including congenital (von Willebrand's disease) or acquired (anti-factor VIII antibodies) disorders
  * Large pleural effusions
  * Psychiatric illness or social situation that would preclude study compliance
* More than 7 days since prior and no concurrent CYP3A4 inducers or inhibitors
* No other concurrent investigational agents

Primary outcomes:
measure: Median Overall Survival
timeFrame: assessed up to 24 months
Secondary outcomes:
measure: Objective Response Rate (Complete Response, Partial Response, or Stable Disease), Evaluated Using the New International Criteria Proposed by the RECIST Committee
timeFrame: Up to 5 years
measure: Median Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Gait Speed
timeFrame: baseline
measure: Gait Speed
timeFrame: at 8 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
Study officials:
affiliation: Case Western Reserve University
name: Charles Nock
role: PRINCIPAL_INVESTIGATOR
References: