Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-Adenoid Cystic Malignant Salivary Tumors

Inclusion Criteria:

- Histologically or cytologically confirmed malignant salivary gland tumor, including
one of the following histologic subtypes:

- Adenoid cystic carcinoma (ACC)

- c-KIT overexpression, defined as CD 117 staining by IHC in 25% of tumor
cells

- Non-ACC

- c-KIT overexpression is not required

- Not amenable to potentially curative surgery or radiotherapy

- Evidence of disease progression (i.e., objective growth of existing tumors) within
the past 4 months

- Radiographically measurable disease, defined as ≥ 1 lesion that can be accurately
measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques or as ≥ 10 mm with
spiral CT scan

- No active pleural or pericardial effusion of any grade

- 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

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- WBC count ≥ 3,000/mm^3

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Serum calcium ≤ 12.0 mg/dL

- Total serum bilirubin normal

- AST/ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No QTc prolongation (defined as a QTc interval ≥ 500 msec), serious ventricular
arrhythmia (ventricular fibrillation or ventricular tachycardia ≥ 3 beats in a row),
or other significant ECG abnormalities

- None of the following conditions:

- Serious or non-healing wound, ulcer, or bone fracture

- Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal
abscesses within the past 28 days

- Cerebrovascular accident or transient ischemic attack within the past 12 months

- Myocardial infraction, cardiac arrhythmia, stable/unstable angina, symptomatic
congestive heart failure, or coronary/peripheral artery bypass graft or stenting
within the past 6 months

- Pulmonary embolism within the past 12 months

- Ejection fraction < 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)

- No condition that would impair the ability to swallow and retain dasatinib tablets
(e.g., GI tract disease resulting in an inability to take oral medication,
requirement for IV alimentation, or active peptic ulcer disease)

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Psychiatric illness or social situation that would limit compliance with study
requirements

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to dasatinib

- No diagnosis of second malignancy within the past 5 years except for fully treated
basal cell carcinoma, squamous cell skin cancer , stage I carcinoma, or adequately
treated in situ carcinoma with no evidence of recurrent disease within the past 12
months

- Recovered from prior therapy

- No prior treatment with any other targeted agents that inhibit VEGFR, BCRABL, c-Src,
c-KIT, PDGFβ receptor, or EPHA2 (e.g., imatinib mesylate)

- No prior surgical procedures affecting absorption

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy

- At least 4 weeks since prior major surgery

- More than 7 days since prior and no concurrent agents with proarrhythmic potential

- More than 7 days since prior and no concurrent potent CYP3A4 inhibitors (e.g.,
ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir,
indinavir, nelfinavir, saquinavir, telithromycin, voriconazole, or nefazodone)

- At least 5 half-lives since prior and no concurrent medications that may cause QTc
prolongation

- No concurrent potent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine,
rifampin, phenobarbital, St. John wort's, aminoglutethimide, primidone, rifabutin,
nevirapine, oxcarbazepine, rifapentine, fosphenytoin, or pentobarbital)

- No other concurrent investigational agents

- No concurrent enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or
phenytoin)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent grapefruit or grapefruit juice

- No other concurrent anticancer agents or therapies