Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Translational Oncology Research International
ClinicalTrials.gov Identifier:
NCT01234935
First received: November 1, 2010
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving dasatinib together with gemcitabine hydrochloride is more effective than gemcitabine hydrochloride alone in treating pancreatic cancer. PURPOSE: This randomized phase II trial is studying how well giving dasatinib together with gemcitabine hydrochloride works compared to giving gemcitabine hydrochloride alone in treating patients with pancreatic cancer previously treated with surgery.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Stage III Pancreatic Cancer
Drug: dasatinib
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Genetic: mutation analysis
Genetic: nucleic acid sequencing
Other: immunohistochemistry staining method
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Randomized, Phase II Trial of Adjuvant Dasatinib Plus Gemcitabine Versus Single-Agent Gemcitabine in Patients With Resected Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Translational Oncology Research International:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: At 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: follow-up every 3 months for 30 months from first treatment or until disease recurrence or withdrawal of consent ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: at 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 126
Study Start Date: October 2010
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • LY-188011
Other: laboratory biomarker analysis
Correlative studies
Genetic: mutation analysis
Correlative studies
Genetic: nucleic acid sequencing
Correlative studies
Other Names:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Experimental: Arm II
Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15 and oral dasatinib once daily on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: *Courses with dasatinib repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • LY-188011
Other: laboratory biomarker analysis
Correlative studies
Genetic: mutation analysis
Correlative studies
Genetic: nucleic acid sequencing
Correlative studies
Other Names:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry

Detailed Description:

PRIMARY OBJECTIVES: I. To compare disease-free survival at 18 months between dasatinib-gemcitabine combination therapy and single-agent gemcitabine. SECONDARY OBJECTIVES: I. To evaluate effects on disease-free survival of the dasatinib-gemcitabine combination therapy compared with gemcitabine alone for adjuvant treatment of resected pancreatic adenocarcinoma. II. To evaluate effects on overall survival of dasatinib-gemcitabine combination therapy compared with gemcitabine alone for adjuvant treatment of resected pancreatic adenocarcinoma. III. To evaluate tolerability and safety of the two arms. IV. To identify potential biological correlates associated with clinical benefit to dasatinib-gemcitabine combination therapy compared with gemcitabine alone. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15 and oral dasatinib once daily on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: * Courses with dasatinib repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent before beginning any protocol specified procedures
  • Histologically proven pancreatic adenocarcinoma
  • Any T, any N, M0 disease that has had all gross disease resected (R0 or R1 resection)
  • ECOG Performance status index 0 or 1
  • Absolute Neutrophils >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 2.0 x UNL; subjects with Gilbert's syndrome, confirmed by genotyping or invader UGTIA1 molecular assay before study entry must have total bilirubin < 3 x UNL
  • ASAT (SGOT) and ALAT (SGPT) =< 2.5 x UNL
  • Alkaline Phosphatase =< 5 x UNL
  • Creatinine < 1.5 x UNL
  • Serum Na, K+, Magnesium, Phosphate and Calcium >= LNL
  • First study treatment must be given within 60 days after surgery and within 7 days after randomization
  • Patients must be accessible for treatment and follow-up and compliant with study procedures
  • Negative pregnancy test (urine or serum) within 7 days before first study treatment for all women of childbearing potential, whom also must implement adequate non-hormonal contraceptive measures during study treatment and for at least 3 months after the last dose of study therapy
  • Ability to take oral medication (dasatinib must be swallowed whole)

Exclusion Criteria:

  • Prior or concurrent systemic anticancer therapy (immunotherapy, hormonal therapy, biological therapy, or chemotherapy) for pancreatic cancer
  • Prior or concurrent radiation therapy for pancreatic cancer
  • Pregnant or lactating patients
  • M1 pancreatic cancer
  • Concurrent congestive heart failure, unstable angina pectoris, or M1 within the 6 months before first study treatment
  • Uncontrolled hypertension or high-risk uncontrolled arrhythmias
  • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
  • Diagnosed or suspected congenital long QT syndrome
  • Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
  • History of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
  • Past or current history of neoplasm other than pancreatic adenocarcinoma, except for: curatively treated non-melanoma skin cancer; in situ carcinoma of the cervix; other cancer curatively treated and with no evidences of disease for at least 1 year
  • Concurrent treatment with other experimental drugs or treatment with investigational drugs within 30 days of first study treatment
  • Currently receiving drugs with known significant CYP 3A4 inhibitory effects (such as ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil, ritonavir, indinavir)
  • Concurrent administration with inducers of CYP 3A4 may result in a lower exposure to dasatinib and are therefore not allowed (e.g., phenytoin, carbamazepine, rifampicin, phenobarbital, pentobarbital, or St John's Wort)
  • Known allergy reactions to dasatinib or gemcitabine or excipients used in the study
  • History of significant bleeding disorders unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., Von Willebrand's disease); diagnosed acquired bleeding disorder within 1 year (e.g., acquired anti-factor VIII antibodies); ongoing or recent (=< 3 months) significant gastrointestinal bleeding
  • Patients currently taking drugs that are generally accepted to have a risk of causing Torsades De Pointes including: quinidine, procainamide, disopyramide; amiodarone, sotalol, ibutilide, dofetilide; erythromycins, clarithromycin; chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide; cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
  • Concurrent treatment with intravenous bisphosphonates; prior treatment should be stopped at least 2 weeks before first dose of study treatment
  • Concurrent medical condition which may increase the risk of toxicity, including pleural or pericardial effusion or any grade
  • Active uncontrolled infection requiring parenteral antimicrobials
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234935

Locations
United States, California
Central Hematology Oncology Medical Group, Inc.
Alhambra, California, United States, 91801
TORI FULLERTON (St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center)
Fullerton, California, United States, 92835
Pacific Shores Medical Group
Long Beach, California, United States, 90813
UCLA medical center
Los Angeles, California, United States, 90024-3417
Translational Oncology Research International (TORI) Network
Los Angeles, California, United States, 90095
TORI NORTHRIDGE (North Valley Hematology/Oncology Medical Group)
Northridge, California, United States, 91325
UCLA Pasadena
Pasadena, California, United States
TORI Inland Valley (Wilshire Oncology Medical Group, Inc. )
Pomona, California, United States, 91767
TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)
Redondo Beach, California, United States, 90277
TORI SANTA BARBARA I (Santa Barbara Hematology Oncology Medical Group, Inc.)
Santa Barbara, California, United States, 93105
TORI SANTA BARBARA II (SANSUM Clinic)
Santa Barbara, California, United States, 93105
TORI SANTA MARIA (Central Coast Medical Oncology Corporation)
Santa Maria, California, United States, 93454
UCLA Valencia
Valencia, California, United States
United States, Georgia
Suburban Hematology-Oncology Associates, P.A.
Lawrenceville, Georgia, United States, 30045
Northwest Georgia Oncology Centers, P.C.
Marietta, Georgia, United States, 30060
United States, Maryland
Chevy Chase Healthcare Management, LLC
Chevy Chase, Maryland, United States, 20815
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89109
Sponsors and Collaborators
Translational Oncology Research International
Investigators
Principal Investigator: Richard Finn Translational Oncology Research International
  More Information

No publications provided

Responsible Party: Translational Oncology Research International
ClinicalTrials.gov Identifier: NCT01234935     History of Changes
Other Study ID Numbers: TRIO-TORI PA-01, NCI-2010-02190
Study First Received: November 1, 2010
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Acinar Cell
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Dasatinib
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014