Clinical trial NCT00859937: Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors
Official title: Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-adenoid Cystic Malignant Salivary Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Salivary Gland Neoplasm
Recurrent Salivary Gland Carcinoma
Salivary Gland Adenoid Cystic Carcinoma
Stage IV Major Salivary Gland Cancer AJCC v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-03-11
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well dasatinib works in treating patients with malignant salivary gland tumors that have come back after treatment or have spread to other parts of the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the objective response rate (complete response plus partial response) of dasatinib in adenoid cystic carcinoma (ACC).

II. Determine the progression-free survival of dasatinib in ACC.

SECONDARY OBJECTIVES:

I. Determine the duration of response. II. Determine the stable disease rate and duration of stable disease. III. Determine progression-free survival. IV. Determine the median survival. V. Determine the overall survival. VI. Determine the safety and tolerability.

TERTIARY OBJECTIVES:

I. To examine biomarkers that relate to SRC proto-oncogene, non-receptor tyrosine kinase (Src) signal transduction and to correlate these biomarkers with clinical response to dasatinib in ACC and non-ACC malignant salivary gland tumors (MSGT).

II. Determine if activating mutations in platelet-derived growth factor alpha polypeptide (PDGFA) and KIT are associated with response in ACC.

OUTLINE:

Patients receive dasatinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed at 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed malignant salivary gland tumor (MSGT), including one of the following histologic subtypes:

  * Adenoid cystic carcinoma (ACC) with c v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit) overexpression or non-ACC MSGT that is not amenable to potentially curable surgery or radiation

    * c-KIT overexpression in ACC patients is defined as cluster of differentiation (CD) 117 staining by immunohistochemistry (IHC) in 25% of tumor cells
    * No stipulation for c-KIT overexpression is not required for non-ACC MSGT patients
* Patients must have radiographically measurable disease; radiographically measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
* Patients must have evidence of disease progression (objective growth of existing tumors) within 4 months of study entry
* No known brain metastases, unless patient meets both of the following criteria:

  * Neurologic status stable for \>= 8 weeks after completion of definitive local therapy (surgery or radiotherapy)
  * No neurologic dysfunction that would confound study results
* Life expectancy greater than 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2 OR Karnofsky performance status (PS) \>= 60%
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelet \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL
* Serum calcium =\< 12.0 mg/dL
* Total serum bilirubin within normal institutional limits
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving dasatinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery
* Patients may not be receiving any other investigational agents
* No prior treatment with any other targeted agents that inhibit vascular endothelial growth factor receptor (VEGFR), Breakpoint cluster region (BCR) ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL), c-Src, c-KIT, platelet-derived growth factor (PDGF) beta receptor, or ephrin type-A receptor 2 (EPHA2) (e.g., imatinib mesylate)
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib
* Patients with corrected QT interval (QTc) prolongation (defined as a QTc interval equal to or greater than 500 msec), serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia greater than or equal to 3 beats in a row) or other significant echocardiogram (ECG) abnormalities are excluded
* Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for intravenous \[IV\] alimentation, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
* Patients with any of the following conditions are excluded:

  * Serious or non-healing wound, ulcer, or bone fracture
  * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses within the past 28 days
  * Any history of cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months
  * History of myocardial infraction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 6 months
  * History of pulmonary embolism within the past 12 months
  * Ejection fraction less than institutional normal by echocardiograph (only required for patients with a known history of congestive heart failure, low ejection fraction, or clinical symptoms/findings consistent with congestive heart failure)
* Patients taking medications that are potent inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme will be determined following a review of their case by the Principal Investigator; every effort should be made to switch patients taking such agents or substances to other medications
* Patients with known brain metastases should be excluded; patients with brain metastases with stable neurologic status following local therapy (surgery or radiation) for at least 8 weeks from definitive therapy and without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events are eligible for participation; patients cannot be receiving enzyme inducing anti-convulsants including carbamazepine, phenobarbital, and phenytoin
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dasatinib
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
* Patients who have an active pleural or pericardial effusion of any grade
* Diagnosis of any second malignancy within the last 5 years; basal cell carcinoma, squamous cell skin cancer, stage I carcinoma fully treated, or in situ carcinoma that have been adequately treated with no evidence of recurrent disease for 12 months will be eligible

Primary outcomes:
measure: Response Rate
timeFrame: Up to 2 months
measure: Progression-free Survival
timeFrame: up to 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 5 years
measure: Changes in Laboratory Correlates
timeFrame: Baseline and 4 weeks
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Merced
country: United States
facility: Mercy UC Davis Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Oncology Care Associates PLLC
state: Michigan
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center-Wakefield Campus
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Hotel Dieu de Montreal
state: Quebec
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Stuart Wong
role: PRINCIPAL_INVESTIGATOR
References: