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

Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors
This study is ongoing, but not recruiting participants.

First Received on March 10, 2009.  
Last Updated on August 15, 2012  
History of Changes
Sponsor: University of Chicago
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00859937
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with recurrent or metastatic malignant salivary gland tumors.

Condition Intervention Phase
Head and Neck Cancer Drug: dasatinib
Genetic: gene expression analysis
Genetic: gene rearrangement analysis
Genetic: mutation analysis
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

  • Response rate [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Toxicity [ Designated as safety issue: Yes ]
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Correlation between Src signal transduction biomarkers and clinical response to dasatinib [ Designated as safety issue: No ]
  • Relationship between activating mutations in PDGFA and KIT and response to dasatinib [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: March 2009
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • Determine the duration of response in patients with non-ACC or c-KIT-expressing ACC of the salivary gland.
  • Determine the stable disease rate and duration of stable disease in these patients.
  • Determine the median survival of these patients.
  • Determine the overall survival of these patients.
  • Determine the safety and tolerability of dasatinib in these patients.
  • Determine the progression-free survival of patients with non-ACC of the salivary gland.

Tertiary

  • 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.
  • 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 for at least 8 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00859937

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Evanston Hospital
Evanston, Illinois, United States, 60201-1781
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology-Hematology Associates, Limited – West
Joliet, Illinois, United States, 60435
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Oncology Hematology Associates of Central Illinois, PC – Peoria
Peoria, Illinois, United States, 61615-7828
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 62701
United States, Indiana
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46885-5099
CCOP – Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
Oncology Care Associates, PLLC
Saint Joseph, Michigan, United States, 49085
United States, Missouri
David C. Pratt Cancer Center at St. John’s Mercy
Saint Louis, Missouri, United States, 63141
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6307
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CHUM – Hotel Dieu Hospital
Montreal, Quebec, Canada, H2L-4M1
Sponsors and Collaborators
University of Chicago
Investigators
Study Chair: Stuart J. Wong, MD Medical College of Wisconsin
  More Information

Additional Information:

No publications provided

Responsible Party: Everett E. Vokes, University of Chicago Cancer Research Center
ClinicalTrials.gov Identifier: NCT00859937    
History of Changes
Other Study ID Numbers: CDR0000636685, UCCRC-16691B
Study First Received: March 10, 2009
Last Updated: August 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IV salivary gland cancer
recurrent salivary gland cancer
salivary gland adenoid cystic carcinoma
high-grade salivary gland mucoepidermoid carcinoma
salivary gland adenocarcinoma
salivary gland anaplastic carcinoma
salivary gland malignant mixed cell type tumor
salivary gland poorly differentiated carcinoma
salivary gland squamous cell carcinoma
low-grade salivary gland mucoepidermoid carcinoma
salivary gland acinic cell tumor

Additional relevant MeSH terms:

Carcinoma, Adenoid Cystic
Head and Neck Neoplasms
Salivary Gland Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2012

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