Clinical trial NCT01234935: Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Translational Oncology Research International
Sponsor class: OTHER
First posted: 2010-11-04
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Disease-free survival
timeFrame: At 18 months
Secondary outcomes:
measure: Overall survival
timeFrame: follow-up every 3 months for 30 months from first treatment or until disease recurrence or withdrawal of consent
measure: Disease-free survival
timeFrame: at 18 months
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Fullerton
country: United States
facility: TORI FULLERTON (St. Jude Heritage Healthcare Virginia K. Crosson Cancer Center)
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA medical center
state: California
city: Los Angeles
country: United States
facility: Translational Oncology Research International (TORI) Network
state: California
city: Northridge
country: United States
facility: TORI NORTHRIDGE (North Valley Hematology/Oncology Medical Group)
state: California
city: Pasadena
country: United States
facility: UCLA Pasadena
state: California
city: Pomona
country: United States
facility: TORI Inland Valley (Wilshire Oncology Medical Group, Inc. )
state: California
city: Redondo Beach
country: United States
facility: TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)
state: California
city: Santa Barbara
country: United States
facility: TORI SANTA BARBARA I (Santa Barbara Hematology Oncology Medical Group, Inc.)
state: California
city: Santa Barbara
country: United States
facility: TORI SANTA BARBARA II (SANSUM Clinic)
state: California
city: Santa Maria
country: United States
facility: TORI SANTA MARIA (Central Coast Medical Oncology Corporation)
state: California
city: Valencia
country: United States
facility: UCLA Valencia
state: California
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates, P.A.
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, P.C.
state: Georgia
city: Chevy Chase
country: United States
facility: Chevy Chase Healthcare Management, LLC
state: Maryland
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
Study officials:
affiliation: Translational Oncology Research International
name: Richard Finn
role: PRINCIPAL_INVESTIGATOR
References: