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

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ClinicalTrials.gov Identifier: NCT00859937
Recruitment Status : Active, not recruiting
First Posted : March 11, 2009
Results First Posted : April 3, 2015
Last Update Posted : November 3, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well dasatinib works in treating patients with recurrent or metastatic malignant salivary gland tumors. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
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 Drug: dasatinib Other: laboratory biomarker analysis Phase 2

Detailed Description:


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2009
Primary Completion Date : January 2013

Arm Intervention/treatment
Experimental: Arm I
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel
Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 2 months ]
    Response rate is percentage of the best overall response which recoded from the start of the treatment until diseases progression/recurrence. Response criteria are defined using the international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee: Complete Response, Disappearance of all target lesions; Partial Response, >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

  2. Progression-free Survival [ Time Frame: up to 5 years ]
    Progression-free survival from start of treatment to the time of disease progression or death from any cause was estimated using the Kaplan-Meier method.

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 5 years ]
    Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.

  2. Changes in Laboratory Correlates [ Time Frame: Baseline and 4 weeks ]
    Changes in laboratory correlates pre-post therapy will be analyzed using paired t-tests. The association between RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorp response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as cova only due to the small sample size) in a Cox regression model of progression-free survival.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00859937

  Show 39 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Stuart Wong University of Chicago

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00859937     History of Changes
Other Study ID Numbers: NCI-2009-01165
NCI-2009-01165 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
16691B ( Other Identifier: University of Chicago )
8271 ( Other Identifier: CTEP )
N01CM00032 ( U.S. NIH Grant/Contract )
P30CA014599 ( U.S. NIH Grant/Contract )
N01CM00038 ( U.S. NIH Grant/Contract )
N01CM00071 ( U.S. NIH Grant/Contract )
First Posted: March 11, 2009    Key Record Dates
Results First Posted: April 3, 2015
Last Update Posted: November 3, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Salivary Gland Neoplasms
Carcinoma, Squamous Cell
Carcinoma, Adenoid Cystic
Carcinoma, Mucoepidermoid
Carcinoma, Acinar Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Neoplasms, Cystic, Mucinous, and Serous
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action