RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have unresectable and/or metastatic salivary gland cancer.

Condition	Treatment or Intervention	Phase
recurrent salivary gland cancer salivary gland adenoid cystic carcinoma stage III salivary gland cancer stage IV salivary gland cancer	Drug: imatinib mesylate  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the antitumor activity of imatinib mesylate, in terms of objective response rates (partial and complete responses) and duration of overall response, in patients with unresectable and/or metastatic adenoid cystic, lymphoepithelioma-like, or myoepithelial salivary gland cancer.
• Determine the safety and tolerability of this drug in these patients.
• Correlate the activity of c-kit and downstream kinases in pre- and post-treatment tumoral biopsies with clinical course in patients treated with this drug.
• Determine the effect of treatment with this drug on tumor samples from these patients in terms of proliferation, apoptosis, and angiogenesis.
• Correlate the steady state levels of this drug achieved with clinical and laboratory correlative endpoints in these patients.
• Determine whether early changes in metabolic activity correlate with molecular changes and predict outcome to therapy in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate twice daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease receive treatment for up to 6 months.

Patients are followed within 3 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 6-19 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenoid cystic, lymphoepithelioma-like, or myoepithelial salivary gland cancer
• Unresectable AND/OR
• Radiologically documented metastatic disease
• c-kit positive tumor (1+, 2+, or 3+)
• At least 1 unidimensionally measurable lesion
• More than 20 mm by conventional techniques OR
• More than 10 mm by spiral CT scan
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic

• Bilirubin less than 1.25 times upper limit of normal (ULN)
• AST/ALT less than 2.5 times ULN

Renal

• Creatinine less than 1.25 times ULN OR
• Creatinine clearance greater than 50 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No congestive heart failure
• No unstable angina
• No active cardiomyopathy
• No unstable ventricular arrhythmias
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study
• No other active malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or non-melanomatous skin cancer
• No uncontrolled psychotic disorders
• No serious infections
• No active peptic ulcer disease
• No other serious medical condition that would preclude study
• No prior allergy to compounds of similar chemical or biologic composition as imatinib mesylate

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent filgrastim (G-CSF)

Chemotherapy

• At least 4 weeks since prior chemotherapy and recovered
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy to sites of measurable disease

Surgery

• At least 4 weeks since prior surgery and recovered

Other

• No other concurrent investigational agents
• No concurrent therapeutic warfarin
• Mini-dose warfarin for prophylaxis or low-molecular weight heparin allowed
• No concurrent erythromycin
• No concurrent acetaminophen doses exceeding 3 g/day

Illinois
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201,  United States
      Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States
      LaGrange Memorial Hospital, LaGrange,  Illinois,  60525,  United States
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61602,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Michigan
      Lakeland Medical Center - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Missouri
      Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
Canada, Ontario
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada

Study chairs or principal investigators

George P. Browman, MD,  Study Chair,  Cancer Care Ontario-Hamilton Regional Cancer Centre   

Study ID Numbers:  CDR0000257029; PMH-PHL-009; NCI-5663
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045669
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08