RATIONALE: Drugs used in chemotherapy, such as BAY 43-9006, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Randomized phase II trial to study the effectiveness of BAY 43-9006 in treating patients who have refractory non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
recurrent non-small cell lung cancer stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer	Drug: sorafenib  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the percent of patients with refractory non-small cell lung cancer maintaining stable disease or objective response after treatment with BAY 43-9006 vs placebo.
• Compare median survival, progression-free survival, and response rate in patients treated with these regimens.
• Correlate ERK and pERK expression with response rate, stable disease, survival, and time to progression in patients treated with these regimens.
• Correlate a pattern of serum proteins present before treatment with BAY 43-9006-related clinical benefits (e.g., response, time to progression, and/or survival) in these patients.
• Correlate plasma levels of adrenomedulin with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to number of prior chemotherapy regimens (2 vs more than 2) and prior epidermal growth factor receptor inhibitor treatment (yes vs no).

• Induction: All patients receive oral BAY 43-9006 twice daily on days 1-28. Treatment continues for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive BAY 43-9006 for up to 1 year in the absence of disease progression.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive oral BAY 43-9006 twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients who develop disease progression within 1 year after randomization cross over to arm I. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 227 patients will be accrued for this study within 17 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC)
• Disease must have progressed after at least 2 prior chemotherapy regimens for NSCLC
• Measurable or nonmeasurable disease
• No prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable and off therapy for at least 2 months

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN (5 times ULN in patients with liver disease)

Renal

• Creatinine less than 1.5 times ULN OR
• Creatinine clearance greater than 50 mL/min

Cardiovascular

• No clinically evident congestive heart failure
• No serious cardiac arrhythmias
• No symptoms of coronary heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically serious active infection
• No other medical condition that would preclude study participation
• No substance abuse that would preclude study participation
• No psychological or social situation that would preclude study participation
• No active second malignancy

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 3 weeks since prior immunotherapy
• No concurrent prophylactic filgrastim (G-CSF)
• No concurrent sargramostim (GM-CSF)

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 3 weeks since prior radiotherapy
• No prior radiotherapy to the only site of measurable or evaluable disease unless there is evidence of disease progression in that site

Surgery

• Not specified

Other

• More than 3 weeks since prior investigational drugs
• Recovered from all prior therapy
• No prior exposure to a ras pathway inhibitor (e.g., farnesyl transferase inhibitor)
• No concurrent CYP3A4 inhibitors or inducers
• No concurrent medications known to be metabolized by the liver with a narrow therapeutic index, including the following:
• Ketoconazole
• Itraconazole
• Quinidine
• Digoxin
• Cyclosporine
• Ritonavir
• Grapefruit products
• Carbamazepine
• Phenytoin
• Phenobarbital
• No other concurrent investigational agents or anticancer therapy

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States
      Veterans Affairs Medical Center - Palo Alto, Palo Alto,  California,  94304-1290,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
      Veterans Affairs Medical Center - Gainesville, Gainesville,  Florida,  32608-1197,  United States
      Veterans Affairs Medical Center - Miami, Miami,  Florida,  33125,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  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
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Iowa
      Burgess Health Center, Onawa,  Iowa,  51040,  United States
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
      Tufts - New England Medical Center, Boston,  Massachusetts,  02111,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417-2399,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States
      Veterans Affairs Medical Center - Omaha, Omaha,  Nebraska,  68105,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cancer Institute of New Jersey at Robert Wood Johnson University Hospital, New Brunswick,  New Jersey,  08903,  United States
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      MBCCOP-Our Lady of Mercy Cancer Center, Bronx,  New York,  10466,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15236,  United States
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
      Veterans Affairs Medical Center - Pittsburgh, Pittsburgh,  Pennsylvania,  15240,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212-2637,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States
Australia, New South Wales
      Westmead Breast Centre at NSW Breast Cancer Institute, Westmead,  New South Wales,  2145,  Australia
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru
Puerto Rico
      MBCCOP - San Juan, San Juan,  00921-3201,  Puerto Rico
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico
      Veterans Affairs Medical Center - San Juan, San Juan,  00927-5800,  Puerto Rico
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Joan Hoff Schiller, MD,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   
William A. Flood, MD,  Milton S. Hershey Medical Center   

Study ID Numbers:  CDR0000315383; ECOG-E250; NCT00064350
Record last reviewed:  January 2005
Last Updated:  January 7, 2005
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00064350
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08