Clinical trial NCT00045669: Imatinib Mesylate in Treating Patients With Salivary Gland Cancer
Official title: A Phase 2 Study Of Imatinib Mesylate In Adenoid Cystic, Lymphoepithelioma-Like And Myoepithelial Salivary Gland Carcinomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: recurrent salivary gland cancer
salivary gland adenoid cystic carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Health Care - Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: LaGrange
country: United States
facility: LaGrange Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
Study officials:
affiliation: Margaret and Charles Juravinski Cancer Centre
name: George P. Browman, MD
role: STUDY_CHAIR
References:
citation: Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL. Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol. 2005 Jan 20;23(3):585-90. doi: 10.1200/JCO.2005.06.125.