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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 : Completed
First Posted : March 11, 2009
Results First Posted : April 3, 2015
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 10, 2009
First Posted Date  ICMJE March 11, 2009
Results First Submitted Date  ICMJE June 19, 2014
Results First Posted Date  ICMJE April 3, 2015
Last Update Posted Date April 20, 2018
Actual Study Start Date  ICMJE March 16, 2009
Actual Primary Completion Date January 30, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2009)
  • Response rate
  • Progression-free survival
Change History Complete list of historical versions of study NCT00859937 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
  • Overall Survival [ Time Frame: Up to 5 years ]
    Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2009)
  • Toxicity
  • Time to progression
  • Overall Survival
  • Correlation between Src signal transduction biomarkers and clinical response to dasatinib
  • Relationship between activating mutations in PDGFA and KIT and response to dasatinib
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors
Official Title  ICMJE Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-adenoid Cystic Malignant Salivary Tumors
Brief Summary This phase II trial is studying how well dasatinib works in treating patients with malignant salivary gland tumors that have come back after treatment or have spread to other parts of the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Salivary Gland Neoplasm
  • Recurrent Salivary Gland Carcinoma
  • Salivary Gland Adenoid Cystic Carcinoma
  • Stage IV Major Salivary Gland Cancer AJCC v7
Intervention  ICMJE
  • Drug: Dasatinib
    Given PO
    Other Names:
    • BMS-354825
    • Sprycel
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE Experimental: Arm I
Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Dasatinib
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2015)
55
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2009)
65
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date January 30, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00859937
Other Study ID Numbers  ICMJE NCI-2009-01165
NCI-2009-01165 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000636685
UCCRC-16691B
16691B ( Other Identifier: University of Chicago Comprehensive Cancer Center )
8271 ( Other Identifier: CTEP )
N01CM00032 ( U.S. NIH Grant/Contract )
N01CM00038 ( U.S. NIH Grant/Contract )
N01CM00071 ( U.S. NIH Grant/Contract )
P30CA014599 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stuart Wong University of Chicago Comprehensive Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP