RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with doxorubicin may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of bortezomib followed by the addition of doxorubicin at the time of disease progression in treating patients who have locally advanced, recurrent, or metastatic adenoid cystic carcinoma (cancer) of the head and neck.

Condition	Treatment or Intervention	Phase
lip and oral cavity cancer Salivary Gland Cancer	Drug: bortezomib  Drug: doxorubicin  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the objective tumor response in patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck treated with bortezomib.

Secondary

• Determine the time to progression in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.
• Determine the toxic effects of this drug in these patients.
• Determine the objective tumor response, time to progression, and overall survival of patients who progress on single-agent bortezomib and are then treated with doxorubicin and bortezomib.
• Determine the toxic effects of this regimen in these patients.
• Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.
• Correlate the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway (NF-kB, p53, p27, cyclin D1, cyclin E, vascular endothelial growth factor [VEGF], MVD, V-CAM, and N-CAM) on tumor tissue with the clinical activity of bortezomib in these patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 8 years.

PROJECTED ACCRUAL: A total of 23-37 patients will be accrued for this study within 2.3 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenoid cystic carcinoma of the head and neck
• Locally advanced, recurrent, or metastatic disease that is considered incurable by known therapies
• Unidimensionally measurable disease
• Must not have stable disease for at least 9 months before study entry
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST and ALT no greater than 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• LVEF at least lower limit of normal by MUGA
• No history of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active or ongoing infection
• No prior allergy to compounds of similar chemical or biological composition to bortezomib
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• No pre-existing neuropathy > grade 1
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Chemotherapy

Chemotherapy

• No prior anthracyclines, including any of the following:
• Doxorubicin
• Epirubicin
• Daunorubicin
• Idarubicin
• No prior mitoxantrone
• No prior high-dose chemotherapy for bone marrow transplantation
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• At least 3 weeks since prior surgery

Other

• More than 4 weeks since prior investigational drugs
• No other concurrent anticancer therapy or agents

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States; Recruiting
      Veterans Affairs Medical Center - Palo Alto, Palo Alto,  California,  94304-1290,  United States; Recruiting
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-3289,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting
      Veterans Affairs Medical Center - Gainesville, Gainesville,  Florida,  32608-1197,  United States; Recruiting
      Veterans Affairs Medical Center - Miami, Miami,  Florida,  33125,  United States; Recruiting
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States; Recruiting
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States; Recruiting
Iowa
      Burgess Health Center, Onawa,  Iowa,  51040,  United States; Recruiting
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States; Recruiting
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States; Recruiting
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
      Cancer Center at Tufts - New England Medical Center, Boston,  Massachusetts,  02111,  United States; Recruiting
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417-2399,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States; Recruiting
      Veterans Affairs Medical Center - Omaha, Omaha,  Nebraska,  68105,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08903,  United States; Recruiting
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States; Recruiting
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States; Recruiting
      MBCCOP-Our Lady of Mercy Cancer Center, Bronx,  New York,  10466,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States; Recruiting
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States; Recruiting
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15236,  United States; Recruiting
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States; Recruiting
      Veterans Affairs Medical Center - Pittsburgh, Pittsburgh,  Pennsylvania,  15240,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States; Recruiting
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212-2637,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States; Recruiting
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States; Recruiting
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States; Recruiting
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia; Recruiting
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru; Recruiting
Puerto Rico
      MBCCOP - San Juan, San Juan,  00921-3201,  Puerto Rico; Recruiting
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico; Recruiting
      Veterans Affairs Medical Center - San Juan, San Juan,  00927-5800,  Puerto Rico; Recruiting
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa; Recruiting

Study chairs or principal investigators

Athanassios Argiris, MD,  Study Chair,  Robert H. Lurie Cancer Center   
Barbara A. Burtness, MD,  Yale Cancer Center   

Study ID Numbers:  CDR0000350319; ECOG-E1303; NCT00077428
Record last reviewed:  November 2004
Last Updated:  April 5, 2005
Record first received:  February 10, 2004
ClinicalTrials.gov Identifier:  NCT00077428
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08