Dasatinib in Treating Patients With Metastatic Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00474812
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arm: 1
• Duration (Months): 81.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: dasatinib; Procedure: laboratory biomarker analysis; Procedure: physiologic testing	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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

2. 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.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Dasatinib (BMS-354825) in Patients With Metastatic Adenocarcinoma of the Pancreas
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib Treatment Patients receive oral dasatinib twice daily on days 1-28.	Drug: dasatinib; Other Names: BMS-354825 Sprycel ; Procedure: laboratory biomarker analysis; Correlative study; Procedure: physiologic testing; Correlative study; Other Names: study of physiologic variables

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. Gait Speed [baseline]

   Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Case Western Reserve University	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Charles Nock, Case Western Reserve University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00474812
• Other Study ID Numbers: NCI-2009-00228; NCI-2009-00228; CDR0000546554; CASE 5206; CASE 5206; 7828; U01CA062502
• First Posted: May 17, 2007
• Last Update Posted: May 5, 2015
• Last Verified: Nov 1, 2013

• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Dasatinib

Study Results

Participant Flow

Recruitment Details	Patients were recruited from Cleveland, Ohio area hospitals, Case Medical Center University Hospitals and MetroHealth Medical Center.

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Period Title: Overall Study
STARTED	51
COMPLETED	44
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Overall Participants	51
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	34 66.7%
Male	17 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 7.8%
White	46 90.2%
More than one race	0 0%
Unknown or Not Reported	1 2%
Region of Enrollment (participants) [Number]
United States	51 100%

Outcome Measures

1. Primary Outcome

Title	Median Overall Survival
Description	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
Time Frame	assessed up to 24 months

Outcome Measure Data

Analysis Population Description

Intent to treat.

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Measure Participants	51
Median (95% Confidence Interval) [months]	4.7

2. Secondary Outcome

Title	Objective Response Rate (Complete Response, Partial Response, or Stable Disease), Evaluated Using the New International Criteria Proposed by the RECIST Committee
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients that reached first scans at 2 months

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Measure Participants	34
Progressive disease	24 47.1%
Stable Disease	10 19.6%

3. Secondary Outcome

Title	Median Progression Free Survival (PFS)
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Measure Participants	51
Median (95% Confidence Interval) [months]	2.1

4. Secondary Outcome

Title	Gait Speed
Description	Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Participants who were ambulatory at baseline

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Measure Participants	17
Mean (Standard Error) [meters per second]	4.1 (0.32)

5. Secondary Outcome

Title	Gait Speed
Description	Gait speed, determined by a 4 meter walk along a properly measured stretch of hallway while being timed with a stopwatch.
Time Frame	at 8 weeks

Outcome Measure Data

Analysis Population Description

Participants who were ambulatory at 8 weeks

Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
Measure Participants	10
Mean (Standard Error) [meters per second]	4.6 (0.64)

Adverse Events

Time Frame	Adverse Events that occur during treatment or within 30 Days of the last dose. The time frames for patients was 0-23 months.
Arm/Group Title	Dasatinib Treatment
Arm/Group Description	Patients receive oral dasatinib twice daily on days 1-28.
All Cause Mortality
	Dasatinib Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib Treatment
	Affected / at Risk (%)	# Events
Total	21/51 (41.2%)
Cardiac disorders
Cardiac Troponin Increase	1/51 (2%)
Myocardial Infarction	1/51 (2%)
Pericardial Effusion	1/51 (2%)
Sinus bradycardia	1/51 (2%)
Gastrointestinal disorders
Abdominal pain	2/51 (3.9%)
Constipation	1/51 (2%)
Diarrhea	1/51 (2%)
Nausea	2/51 (3.9%)
Small intestinal obstruction	2/51 (3.9%)
Vomiting	2/51 (3.9%)
General disorders
Death not associated with CTCAE term - Death NOS (not otherwise specified)	4/51 (7.8%)
Fever	1/51 (2%)
Pain	1/51 (2%)
Hepatobiliary disorders
Hepatobiliary disorders	2/51 (3.9%)
Hepatobiliary disorders	1/51 (2%)
Infections and infestations
Infections and infestations - Other, NOS	8/51 (15.7%)
Sepsis	2/51 (3.9%)
Metabolism and nutrition disorders
Dehydration	3/51 (5.9%)
Nervous system disorders
Nervous system disorders - Other, NOS	1/51 (2%)
Psychiatric disorders
Depression	1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/51 (2%)
Pneumonitis	1/51 (2%)
Vascular disorders
Thromboembolic event	5/51 (9.8%)
Other (Not Including Serious) Adverse Events
	Dasatinib Treatment
	Affected / at Risk (%)	# Events
Total	50/51 (98%)
Blood and lymphatic system disorders
Anemia	36/51 (70.6%)
Gastrointestinal disorders
Abdominal distension	4/51 (7.8%)
Abdominal pain	34/51 (66.7%)
Constipation	23/51 (45.1%)
Diarrhea	20/51 (39.2%)
Dry mouth	4/51 (7.8%)
Dyspepsia	8/51 (15.7%)
Dysphagia	4/51 (7.8%)
Gastrointestinal disorders - Other, NOS	5/51 (9.8%)
Mucositis oral	5/51 (9.8%)
Nausea	33/51 (64.7%)
Vomiting	25/51 (49%)
General disorders
Chills	8/51 (15.7%)
Edema face	9/51 (17.6%)
Edema limbs	8/51 (15.7%)
Fatigue	39/51 (76.5%)
Fever	8/51 (15.7%)
Investigations
Alanine aminotransferase increased	27/51 (52.9%)
Alkaline phosphatase increased	34/51 (66.7%)
Aspartate aminotransferase increased	35/51 (68.6%)
Blood bilirubin increased	11/51 (21.6%)
Creatinine increased	7/51 (13.7%)
INR increased	3/51 (5.9%)
Lymphocyte count decreased	26/51 (51%)
Platelet count decreased	16/51 (31.4%)
Weight loss	18/51 (35.3%)
White blood cell decreased	12/51 (23.5%)
Metabolism and nutrition disorders
Anorexia	34/51 (66.7%)
Dehydration	15/51 (29.4%)
Hyperglycemia	26/51 (51%)
Hyperkalemia	4/51 (7.8%)
Hypoalbuminemia	31/51 (60.8%)
Hypocalcemia	25/51 (49%)
Hypoglycemia	5/51 (9.8%)
Hypokalemia	18/51 (35.3%)
Hyponatremia	31/51 (60.8%)
Hypophosphatemia	7/51 (13.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/51 (9.8%)
Back pain	13/51 (25.5%)
Generalized muscle weakness	12/51 (23.5%)
Myalgia	4/51 (7.8%)
Pain in extremity	5/51 (9.8%)
Nervous system disorders
Dizziness	8/51 (15.7%)
Dysgeusia	7/51 (13.7%)
Headache	8/51 (15.7%)
Peripheral sensory neuropathy	10/51 (19.6%)
Psychiatric disorders
Agitation	3/51 (5.9%)
Anxiety	7/51 (13.7%)
Confusion	4/51 (7.8%)
Depression	11/51 (21.6%)
Insomnia	18/51 (35.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	9/51 (17.6%)
Skin and subcutaneous tissue disorders
Alopecia	4/51 (7.8%)
Hyperhidrosis	3/51 (5.9%)
Pruritus	3/51 (5.9%)
Rash acneiform	7/51 (13.7%)
Rash maculo-papular	11/51 (21.6%)
Vascular disorders
Hot flashes	7/51 (13.7%)
Hypertension	4/51 (7.8%)
Thromboembolic event	3/51 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.