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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00859937
First received: March 10, 2009
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
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 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From start of treatment to the time of disease progression or death from any cause, assessed up to 4 weeks ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.

  • Changes in laboratory correlates [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Changes in laboratory correlates pre-post therapy will be analyzed using paired t-tests. The association between the presence or absence of RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorphisms in the RET gene and response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as covariates (univariate analyses only due to the small sample size) in a Cox regression model of progression-free survival.


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

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 38 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Stuart Wong University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00859937     History of Changes
Other Study ID Numbers: NCI-2009-01165, NCI-2009-01165, CDR0000636685, UCCRC-16691B, 16691B, 8271, N01CM00071, N01CM00032, N01CM00038
Study First Received: March 10, 2009
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 20, 2014