RATIONALE: Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers.

Condition	Treatment or Intervention	Phase
high-grade salivary gland carcinoma low-grade salivary gland carcinoma Salivary Gland Cancer	Drug: lapatinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the antitumor activity of lapatinib, in terms of objective response rate (partial response [PR] and complete response [CR]), in patients with recurrent and/or metastatic adenoid cystic carcinoma of the salivary gland.

Secondary

• Determine the duration of objective response in patients treated with this drug.
• Determine the rate and duration of stable disease in patients treated with this drug.
• Determine progression-free, median, and overall survival of patients treated with this drug.
• Determine the antitumor activity of this drug, in terms of objective response rate (PR and CR), in patients with other epidermal growth factor receptor- and/or ERBB2-overexpressing malignant tumors of the salivary gland.
• Determine the safety and tolerability of this drug in these patient populations.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 12-67 patients (12-37 patients with adenoid cystic carcinoma [ACC] of the salivary gland and a maximum of 30 patients with epidermal growth factor receptor- or ERBB2-expressing non-ACC of the salivary gland) will be accrued for this study within 18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenoid cystic or other malignant salivary gland carcinoma of major or minor salivary gland origin, meeting 1 of the following criteria:
• Epidermal growth factor receptor (EGFR) expressing tumors
• ERBB2 expressing tumors
• Recurrent and/or metastatic disease
• Progressive disease as defined by 1 of the following criteria occurring within in the past 6 months:
• At least a 20% increase in radiologically or clinically measurable disease
• Appearance of any new lesions
• Deterioration in clinical status
• Not amenable to surgery or curative radiotherapy
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Lesion must be outside of field of prior local therapy OR disease has progressed within the treatment field
• No known brain metastases
• Tumor lesions accessible for biopsy
• In the event that tumor biopsy is medically contraindicated exceptions may be granted by the Principal Investigator only

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• Cardiac ejection fraction normal by echocardiogram or MUGA
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• Able to swallow and retain oral medication
• No gastrointestinal disease resulting in an inability to take oral medication
• No malabsorption syndrome
• No requirement for IV alimentation
• No uncontrolled inflammatory gastrointestinal disease (e.g., Crohn's disease or ulcerative colitis)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing and able to undergo tumor biopsy (unless medically contraindicated)
• No other active malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to lapatinib
• No other uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy, except low-dose, non-myelosuppressive radiotherapy

Surgery

• No prior gastrointestinal surgical procedures affecting absorption
• At least 4 weeks since prior surgery

Other

• Recovered from all prior therapy
• No prior EGFR or ERBB2-targeting therapies
• At least 7 days since prior and no concurrent CYP3A4 inhibitors
• At least 7 days since prior and no concurrent proton-pump inhibitors or H_2 inhibitors
• At least 14 days since prior and no concurrent CYP3A4 inducers
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
District of Columbia
      Howard University Cancer Center at Howard University Hospital, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      Oncology Care Associates, P.L.L.C., Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States; Recruiting
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
      Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus, Ottawa,  Ontario,  K1H 8L6,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting

Study chairs or principal investigators

Lillian L. Siu, MD, FRCPC,  Principal Investigator,  Princess Margaret Hospital   

Study ID Numbers:  CDR0000394174; PMH-PHL-028; NCI-6701; NCT00095563
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  November 5, 2004
ClinicalTrials.gov Identifier:  NCT00095563
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08