Dasatinib in Treating Patients With Stage IV Pancreatic Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00544908
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 7
• Locations: 2
• Arm: 1
• Patients Per Site: 3.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: dasatinib; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Dasatinib in Patients With Metastatic Pancreatic Cancer
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib Dasatinib 70 mg po bid (1 cycle=28 days)	Drug: dasatinib; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) Rate at 4 Months [Four months.]

   Progressive disease - appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the treating physician should prevail and the progression status should be confirmed later on by a review panel (or study chair/primary investigator).

Secondary Outcome Measures

1. Response Rate [After every two cycles, up to 5 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Eligibility Criteria

Criteria

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

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	City of Hope Medical Group	Pasadena	California	United States	91105

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Vincent Chung, MD, City of Hope Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT00544908
• Other Study ID Numbers: 07024; P30CA033572; CHNMC-07024; BMS-CA180-114; CDR0000570288
• First Posted: Oct 16, 2007
• Last Update Posted: Oct 5, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by City of Hope Medical Center: stage IV pancreatic cancer
• Additional relevant MeSH terms: Pancreatic Neoplasms; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg po bid (1 cycle=28 days)
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg po bid (1 cycle=28 days)
Overall Participants	7
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	4 57.1%
Male	3 42.9%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Rate at 4 Months
Description	Progressive disease - appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the treating physician should prevail and the progression status should be confirmed later on by a review panel (or study chair/primary investigator).
Time Frame	Four months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg po bid (1 cycle=28 days)
Measure Participants	7
Number [percentage of participants]	0 0%

2. Secondary Outcome

Title	Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	After every two cycles, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg po bid (1 cycle=28 days)
Measure Participants	7
Number [percentage of participants]	0 0%

Adverse Events

Time Frame	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Adverse Event Reporting Description	Adverse events recorded over a period of 13 months.
Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg po bid (1 cycle=28 days)
All Cause Mortality
	Dasatinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Gastrointestinal disorders
Diarrhea	1/7 (14.3%)	1
Nausea	1/7 (14.3%)	1
Small intestinal obstruction	1/7 (14.3%)	1
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/7 (14.3%)	1
Metabolism and nutrition disorders
Dehydration	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/7 (71.4%)	6
Cardiac disorders
Sinus bradycardia	1/7 (14.3%)	1
Sinus tachycardia	1/7 (14.3%)	1
Eye disorders
Vitreous hemorrhage	1/7 (14.3%)	1
Gastrointestinal disorders
Abdominal distension	2/7 (28.6%)	2
Abdominal pain	5/7 (71.4%)	5
Constipation	2/7 (28.6%)	3
Diarrhea	1/7 (14.3%)	1
Dry mouth	1/7 (14.3%)	1
Flatulence	1/7 (14.3%)	2
Gastritis	1/7 (14.3%)	1
Ileus	1/7 (14.3%)	1
Nausea	3/7 (42.9%)	3
Vomiting	4/7 (57.1%)	4
General disorders
Disease progression	1/7 (14.3%)	1
Edema limbs	1/7 (14.3%)	1
Fatigue	4/7 (57.1%)	5
Flu-like symptoms	1/7 (14.3%)	1
Irritability	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	1/7 (14.3%)	1
Investigations
Alanine aminotransferase increased	3/7 (42.9%)	4
Alkaline phosphatase increased	4/7 (57.1%)	5
Aspartate aminotransferase increased	4/7 (57.1%)	5
Bilirubin increased	1/7 (14.3%)	1
Creatinine increased	4/7 (57.1%)	4
Lymphocyte count decreased	2/7 (28.6%)	3
Weight loss	1/7 (14.3%)	1
Metabolism and nutrition disorders
Acidosis	1/7 (14.3%)	1
Anorexia	3/7 (42.9%)	4
Blood glucose increased	2/7 (28.6%)	3
Dehydration	4/7 (57.1%)	4
Serum albumin decreased	2/7 (28.6%)	2
Serum calcium decreased	2/7 (28.6%)	2
Serum magnesium increased	1/7 (14.3%)	1
Serum phosphate decreased	1/7 (14.3%)	1
Serum potassium decreased	1/7 (14.3%)	1
Serum sodium decreased	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)	2
Muscle weakness	1/7 (14.3%)	1
Nervous system disorders
Dizziness	2/7 (28.6%)	2
Headache	1/7 (14.3%)	1
Psychiatric disorders
Confusion	1/7 (14.3%)	1
Depression	1/7 (14.3%)	2
Renal and urinary disorders
Bladder hemorrhage	1/7 (14.3%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/7 (28.6%)	2
Hypoxia	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/7 (14.3%)	1
Petechiae	1/7 (14.3%)	1
Vascular disorders
Hypotension	3/7 (42.9%)	3

Limitations/Caveats

Study was terminated early due to toxicity.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.