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

Stage III Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01234935
• Other study ID #: TRIO-TORI PA-01
• Secondary ID: NCI-2010-02190
• Status: Completed
• Phase: Phase 2
• First received: November 1, 2010
• Last updated: January 5, 2018
• Start date: January 13, 2011
• Est. completion date: November 27, 2017

Study information

• Verified date: January 2018
• Source: Translational Oncology Research International
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: November 27, 2017
• Est. primary completion date: November 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acinar Cell Adenocarcinoma of the Pancreas
• Adenocarcinoma
• Duct Cell Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Recurrent Pancreatic Cancer
• Stage IA Pancreatic Cancer
• Stage IB Pancreatic Cancer
• Stage IIA Pancreatic Cancer
• Stage IIB Pancreatic Cancer
• Stage III Pancreatic Cancer

Intervention

Drug:
• dasatinib
Given orally
• gemcitabine hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Genetic:
• mutation analysis
Correlative studies
• nucleic acid sequencing
Correlative studies

Other:
• immunohistochemistry staining method
Correlative studies

Locations

Country	Name	City	State
United States	Central Hematology Oncology Medical Group, Inc.	Alhambra	California
United States	Chevy Chase Healthcare Management, LLC	Chevy Chase	Maryland
United States	TORI FULLERTON (St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center)	Fullerton	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hematology-Oncology Associates, P.A.	Lawrenceville	Georgia
United States	Pacific Shores Medical Group	Long Beach	California
United States	Translational Oncology Research International (TORI) Network	Los Angeles	California
United States	UCLA medical center	Los Angeles	California
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	TORI NORTHRIDGE (North Valley Hematology/Oncology Medical Group)	Northridge	California
United States	UCLA Pasadena	Pasadena	California
United States	TORI Inland Valley (Wilshire Oncology Medical Group, Inc. )	Pomona	California
United States	TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)	Redondo Beach	California
United States	TORI SANTA BARBARA I (Santa Barbara Hematology Oncology Medical Group, Inc.)	Santa Barbara	California
United States	TORI SANTA BARBARA II (SANSUM Clinic)	Santa Barbara	California
United States	TORI SANTA MARIA (Central Coast Medical Oncology Corporation)	Santa Maria	California
United States	UCLA Valencia	Valencia	California

Sponsors (1)

Lead Sponsor	Collaborator
Translational Oncology Research International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival		At 18 months
Secondary	Overall survival		follow-up every 3 months for 30 months from first treatment or until disease recurrence or withdrawal of consent
Secondary	Disease-free survival		at 18 months