Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

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.

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