RATIONALE: Drugs used in chemotherapy such as docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. It is not yet known whether bortezomib is more effective with or without docetaxel in treating patients with advanced non-small cell lung cancer.

PURPOSE: Randomizedphase II trial to compare the effectiveness of bortezomib with or without docetaxel in treating patients who have relapsed or refractorystage IIIB or stage IV non-small cell lung cancer.

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: docetaxel  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the tumor response rates (complete and partial response) in patients with relapsed or refractory advanced non-small cell lung cancer treated with bortezomib with vs without docetaxel.

Secondary

• Compare time to progression in patients treated with these regimens.
• Compare the overall and 1-year survival of patients treated with these regimens.
• Compare the safety and tolerability of these regimens in these patients.
• Compare the pharmacokinetics and pharmacodynamics of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
• Arm II: Patients receive docetaxel IV over 1 hour on day 1 and bortezomib IV as in arm I. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond confirmation of CR.

Quality of life is assessed on day 1 of each treatment course (before drug administration) and at 30 days after the completion of study treatment.

Patients are followed at 30 days and then every 3 months for survival.

PROJECTED ACCRUAL: A total of 155 patients (75 for arm I and 80 for arm II) will be accrued for this study within 1 year.

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
• Locally advanced (stage IIIB) or metastatic (stage IV) disease
• Inoperable disease
• Relapsed or refractory disease
• Received 1, and only 1, prior chemotherapy regimen for locally advanced or metastatic disease
• Measurable or evaluable disease
• No symptomatic or inadequately treated brain metastases
• No CNS disease

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 3 months

Hematopoietic

• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 8.0 g/dL
• Absolute neutrophil count greater than 1,500/mm^3

Hepatic

• AST and ALT less than 3 times upper limit of normal (ULN)
• Bilirubin less than 1.5 times ULN
• Hepatitis B surface antigen negative
• Hepatitis C negative

Renal

• Creatinine less than 1.8 mg/dL

Cardiovascular

• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV heart failure
• No uncontrolled angina
• No severe uncontrolled ventricular arrhythmias
• No electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• No poorly controlled hypertension

Immunologic

• No active systemic infection requiring treatment
• No prior allergic reaction attributable to compounds containing boron or mannitol
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No peripheral neuropathy grade 2 or greater
• No diabetes mellitus
• No other serious medical or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 6 weeks since prior monoclonal antibody therapy
• No concurrent routine use of colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy
• No prior docetaxel
• Prior paclitaxel allowed
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent corticosteroids (e.g., prednisone or prednisolone) except dexamethasone as premedication

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• No concurrent surgery for cancer management or treatment

Other

• More than 5 years since prior treatment for any other cancer except basal cell skin cancer or carcinoma in situ of the cervix
• More than 4 weeks since prior investigational agents
• No prior bortezomib
• No other concurrent investigational agents
• No other concurrent clinical research study participation
• No other concurrent antineoplastic therapy
• No concurrent routine use of anti-inflammatory drugs, including cyclo-oxygenase inhibitors (e.g., celecoxib or rofecoxib)

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35233-2115,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8028,  United States
Florida
      University of Miami Sylvester Cancer Center, Miami,  Florida,  33136,  United States
Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States
Minnesota
      Hubert H. Humphrey Cancer Center at North Memorial Medical Center, Robbinsdale,  Minnesota,  55422,  United States
Missouri
      Kansas City Cancer Centers - Central, Kansas City,  Missouri,  64111,  United States
      Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States
North Carolina
      Blumenthal Cancer Center at Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Pennsylvania
      Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6868,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-5666,  United States

Study chairs or principal investigators

Joan Hoff Schiller, MD,  Principal Investigator,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000305974; WCCC-M34102-048; UCLA-0301037; MILLENNIUM-M34102-048
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00064012
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08