RATIONALE: Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Bortezomib may also help gemcitabine and carboplatin kill more tumor cells by making the cells more sensitive to the drugs.

PURPOSE: Phase II trial to study the effectiveness of combining bortezomib with gemcitabine and carboplatin in treating patients who have advanced or recurrent non-small cell lung cancer that has not been previously treated with chemotherapy.

Condition	Treatment or Intervention	Phase
stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer recurrent non-small cell lung cancer	Drug: bortezomib  Drug: carboplatin  Drug: gemcitabine  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the overall survival of patients with chemotherapy-naïve advanced or recurrent non-small cell lung cancer treated with gemcitabine, carboplatin, and bortezomib.

Secondary

• Determine the response rate (confirmed and unconfirmed, complete and partial) and progression-free survival of patients with measurable disease treated with this regimen.
• Determine the quantitative toxic effects of this regimen in these patients.
• Correlate levels of hypoxia-induced secreted proteins and tumor DNA in plasma, levels of apoptosis-associated proteins in tumor tissue, and the change in levels of bortezomib-modulated proteins in peripheral white blood cells with response and survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive bortezomib alone on the above schedule for up to 1 year at the discretion of the treating physician.

Patients are followed every 6 months for up to 3 years after registration.

PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study within 5 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• One of the following disease stages:
• Selected stage IIIB (T4 due to malignant pleural effusion, any N, M0)
• Stage IV (any T, any N, M1 [distant metastases present])
• Recurrent disease after prior surgery and/or radiotherapy
• Measurable or nonmeasurable disease by CT scan, MRI, or x-ray
• No pleural effusions, ascites, or laboratory parameters as the only evidence of disease
• Disease must be outside the prior radiation field or a new lesion formed inside the port
• No known brain metastases
• Must be offered participation in SWOG-S9925

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• SGOT or SGPT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

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

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No known hypersensitivity to boron, mannitol, or bortezomib
• No greater than grade 1 peripheral neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic agents for NSCLC
• No concurrent biologic agents

Chemotherapy

• No prior systemic chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered

Other

• No other concurrent anticancer agents
• No other concurrent investigational drugs
• No concurrent combination antiretroviral therapy for HIV-positive patients

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States
      Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda,  California,  92357,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Hines (Edward Hines, Junior Hospital), Hines,  Illinois,  60141,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Cancer Institute at Providence Hospital, Southfield,  Michigan,  48075,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
Tennessee
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38104,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Angela Davies, MD,  University of California Davis Cancer Center   
Primo N. Lara, MD,  University of California Davis Cancer Center   

Study ID Numbers:  CDR0000349336; SWOG-S0339
Record last reviewed:  November 2004
Last Updated:  November 4, 2004
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075751
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08