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

November 1, 2010
November 6, 2013
October 2010
October 2014   (final data collection date for primary outcome measure)
Disease-free survival [ Time Frame: At 18 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01234935 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery
A Multicenter, Open-Label, Randomized, Phase II Trial of Adjuvant Dasatinib Plus Gemcitabine Versus Single-Agent Gemcitabine in Patients With Resected Pancreatic Adenocarcinoma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • 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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Other: laboratory biomarker analysis
    • Genetic: mutation analysis
    • Genetic: nucleic acid sequencing
    • Other: immunohistochemistry staining method
  • 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.
    Interventions:
    • Drug: dasatinib
    • Drug: gemcitabine hydrochloride
    • Other: laboratory biomarker analysis
    • Genetic: mutation analysis
    • Genetic: nucleic acid sequencing
    • Other: immunohistochemistry staining method
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
126
Not Provided
October 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01234935
TRIO-TORI PA-01, NCI-2010-02190
Yes
Translational Oncology Research International
Translational Oncology Research International
Not Provided
Principal Investigator: Richard Finn Translational Oncology Research International
Translational Oncology Research International
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP