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

Phase 2
18 Years
Open (Enrolling)
High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Recurrent Salivary Gland Cancer, Salivary Gland Acinic Cell Tumor, Salivary Gland Adenocarcinoma, Salivary Gland Adenoid Cystic Carcinoma, Salivary Gland Anaplastic Carcinoma, Salivary Gland Malignant Mixed Cell Type Tumor, Salivary Gland Poorly Differentiated Carcinoma, Salivary Gland Squamous Cell Carcinoma, Stage IV Salivary Gland Cancer

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Trial Information

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


I. Determine the objective response rate (complete and partial response) in patients with
recurrent or metastatic c-KIT-expressing adenoid cystic carcinoma (ACC) of the salivary
gland treated with dasatinib.

II. Determine the progression-free survival of these patients.


I. Determine the duration of response in patients with non-ACC or c-KIT-expressing ACC of
the salivary gland.

II. Determine the stable disease rate and duration of stable disease in these patients.

III. Determine the median survival of these patients. IV. Determine the overall survival of
these patients. V. Determine the safety and tolerability of dasatinib in these patients. VI.
Determine the progression-free survival of patients with non-ACC of the salivary gland.


I. Correlate biomarkers that relate to Src signal transduction with clinical response to
dasatinib in patients with non-ACC or c-KIT-expressing ACC of the salivary gland.

II. Determine if activating mutations in PDGFA and KIT are associated with response in
patients with c-KIT-expressing ACC of the salivary gland.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 cohorts according to histologic subtype (adenoid cystic
carcinoma [ACC] vs non-ACC).

Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples are collected at baseline for correlative laboratory
biomarker and pharmacogenomic studies. Samples are analyzed for total c-Src and
phosphorylated Src expression by IHC; polymorphisms and gene rearrangements/activating
mutations in PDGFA (within exons 18 and 12) and KIT (within exons 9, 11, 13, and 27) by PCR;
and additional biomarkers associated with Src signal transduction and/or dasatinib response
(e.g., phospho-KIT, phospho-PDGFR, EPHA2, VEGF, Stat3, Bcl-x, survivin, cyclin D1, and
p27_Kip) by IHC.

After completion of study therapy, patients are followed at 4 weeks.

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

- 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

- Ongoing or active infection

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

- 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

- 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

- 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

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent grapefruit or grapefruit juice

- No other concurrent anticancer agents or therapies

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Time Frame:

Up to 4 weeks

Safety Issue:


Principal Investigator

Stuart Wong

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2009

Completion Date:

Related Keywords:

  • High-grade Salivary Gland Mucoepidermoid Carcinoma
  • Low-grade Salivary Gland Mucoepidermoid Carcinoma
  • Recurrent Salivary Gland Cancer
  • Salivary Gland Acinic Cell Tumor
  • Salivary Gland Adenocarcinoma
  • Salivary Gland Adenoid Cystic Carcinoma
  • Salivary Gland Anaplastic Carcinoma
  • Salivary Gland Malignant Mixed Cell Type Tumor
  • Salivary Gland Poorly Differentiated Carcinoma
  • Salivary Gland Squamous Cell Carcinoma
  • Stage IV Salivary Gland Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Carcinoma, Adenoid Cystic
  • Salivary Gland Neoplasms
  • Carcinoma, Acinar Cell
  • Carcinoma, Mucoepidermoid



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