Dasatinib in Treating Patients With Metastatic Pancreatic Cancer

Phase 2

Completed

Conditions: Recurrent Pancreatic Cancer
Adenocarcinoma of the Pancreas
Stage IV Pancreatic Cancer

Interventions: Drug: dasatinib
Procedure: laboratory biomarker analysis
Procedure: physiologic testing

Registration Number: NCT00474812

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dasatinib Treatment	physiologic testing	Patients receive oral dasatinib twice daily on days 1-28.
Dasatinib Treatment	dasatinib	Patients receive oral dasatinib twice daily on days 1-28.
Dasatinib Treatment	laboratory biomarker analysis	Patients receive oral dasatinib twice daily on days 1-28.

Primary Outcome Measures

Name	Time	Method
Median Overall Survival	assessed up to 24 months	From the date of onset of treatment to the date of death and to the date of last follow-up for those still alive, assessed up to 24 months

Secondary Outcome Measures

Name	Time	Method
Median Progression Free Survival (PFS)	Up to 5 years	Number of months patients were free of disease progression, defined as \< 20% increase in the sum of the LD of target lesions nor the appearance of one or more new lesions.
Gait Speed	at 8 weeks	Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch.
Objective Response Rate (Complete Response, Partial Response, or Stable Disease), Evaluated Using the New International Criteria Proposed by the RECIST Committee	Up to 5 years	Response is defined as CR (Complete Response), PR (Partial Response) or SD (Stable Disease) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. SD: neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease (PD). Progressive disease (PD) is defined as: at least a 20% increase in the sum of the LD of target lesions.