Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors
Condition: Malignant Salivary Gland Neoplasm; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IV Major Salivary Gland Cancer AJCC v7
MeSH terms: Carcinoma; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; Recurrence
Intervention: Dasatinib; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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