BAY 43-9006 in Treating Patients With Refractory Non-Small Cell Lung Cancer

BAY 43-9006 is a "targeted drug" specifically engineered to inhibit something called the RAF kinase within the cancer cells. RAF in turn is part of the RAS oncogene pathway. RAS is a gene which drives cell division and is over-expressed in many cancers, including RCC. For more information: http://www.cancerguide.org/rcc_bay43-9006.html

http://www.clinicaltrials.gov/ct/show/NCT00064350?amp;order=7

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: Randomizedphase II trial to study the effectiveness of BAY 43-9006 in treating patients who have refractorynon-small cell lung cancer.

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.

Eligibility

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

Location and Contact Information

Alabama
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama, 35294-3300, United States; Recruiting
Carla I. Falkson, MD 205-975-2691 cfalkson@uab.edu

Arizona
CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale, Arizona, 85259-5404, United States; Recruiting

Tom Robert Fitch, MD 480-301-9875

California
City of Hope Comprehensive Cancer Center, Duarte, California, 91010-3000, United States; Recruiting

Clinical Trials Office - New Patient Services 800-826-4673 becomingapatient@coh.org

Stanford Cancer Center at Stanford University Medical Center, Stanford, California, 94305-5216, United States; Recruiting

Harlan A. Pinto, MD 650-725-9057

Veterans Affairs Medical Center - Palo Alto, Palo Alto, California, 94304-1290, United States; Recruiting

Harlan A. Pinto, MD 650-493-5000 ext. 4948

Colorado
CCOP - Colorado Cancer Research Program, Incorporated, Denver, Colorado, 80224, United States; Recruiting

Eduardo R. Pajon, MD 303-777-2663

Delaware
CCOP - Christiana Care Health Services, Newark, Delaware, 19713, United States; Recruiting

Stephen Scott Grubbs, MD 302-623-4100

District of Columbia
MBCCOP - Howard University Cancer Center, Washington, District of Columbia, 20060, United States; Recruiting

Lucile L. Adams-Campbell, PhD 202-806-7697

Florida
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, 33612-9497, United States; Recruiting

Cancer Answers 800-456-7121 canceranswers@moffitt.usf.edu

Veterans Affairs Medical Center - Gainesville, Gainesville, Florida, 32608-1197, United States; Recruiting

Dean Latain McCarley, MD 352-374-6016

Veterans Affairs Medical Center - Miami, Miami, Florida, 33125, United States; Recruiting

Niramol Savaraj, MD 305-324-3143 nsavaraj@med.miami.edu

Veterans Affairs Medical Center - Tampa (Haley), Tampa, Florida, 33612, United States; Recruiting

Julie A. Kish, MD, FACP 813-972-2000

Georgia
Veterans Affairs Medical Center - Atlanta (Decatur), Decatur, Georgia, 30033, United States; Recruiting

Maria Jose Amarante Ribeiro, MD 404-728-7680 maria.ribeiro@med.va.gov

Winship Cancer Institute of Emory University, Atlanta, Georgia, 30322, United States; Recruiting

William Costin Wood, MD 404-778-5180

Illinois
CCOP - Carle Cancer Center, Urbana, Illinois, 61801, United States; Recruiting

Kendrith M. Rowland, MD 217-383-4083 kendrith.rowland@carle.com

CCOP - Central Illinois, Decatur, Illinois, 62526, United States; Recruiting

James L. Wade, MD 217-876-6617

CCOP - Evanston, Evanston, Illinois, 60201, United States; Recruiting

Gershon Y. Locker, MD, FACP 847-570-2518 glocker@enh.org

CCOP - Illinois Oncology Research Association, Peoria, Illinois, 61602, United States; Recruiting

John W. Kugler, MD 309-636-3605

Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois, 60611, United States; Recruiting

Al Bowen Benson, MD, FACP 312-695-1382

Veterans Affairs Medical Center - Lakeside Chicago, Chicago, Illinois, 60611-4494, United States; Recruiting

Timothy M. Kuzel, MD 312-469-3748

Indiana
CCOP - Northern Indiana CR Consortium, South Bend, Indiana, 46601, United States; Recruiting

Rafat H. Ansari, MD, FACP 574-284-7977

Indiana University Cancer Center, Indianapolis, Indiana, 46202-5289, United States; Recruiting

Patrick J. Loehrer, MD 317-278-7418

Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis, Indiana, 46202, United States; Recruiting

Patrick J. Loehrer, MD 317-554-0000

Iowa
Burgess Health Center, Onawa, Iowa, 51040, United States; Recruiting

James A. Mailliard, MD 712-423-2311

CCOP - Cedar Rapids Oncology Project, Cedar Rapids, Iowa, 52403-1206, United States; Recruiting

Martin Wiesenfeld, MD 319-363-8303

CCOP - Iowa Oncology Research Association, Des Moines, Iowa, 50309-1016, United States; Recruiting

Roscoe F. Morton, MD 515-244-7586

Iowa Lutheran Hospital, Des Moines, Iowa, 50316-2301, United States; Recruiting

Roscoe F. Morton, MD 515-663-5612

John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines, Iowa, 50309, United States; Recruiting

Roscoe F. Morton, MD 515-241-4245

Mercy Cancer Center at Mercy Medical Center-Des Moines, Des Moines, Iowa, 50314, United States; Recruiting

Roscoe F. Morton, MD 515-247-3121

Kansas
CCOP - Wichita, Wichita, Kansas, 67214-3882, United States; Recruiting

Shaker R. Dakhil, MD 316-268-5784

Veterans Affairs Medical Center - Wichita, Wichita, Kansas, 67218, United States; Recruiting

Shaker R. Dakhil, MD 316-685-2221

Louisiana
CCOP - Ochsner, New Orleans, Louisiana, 70121, United States; Recruiting

Carl G. Kardinal, MD 504-842-3910

MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana, 70112, United States; Recruiting

Jill Gilbert, MD 504-568-5151 jgilbe@lsuhsc.edu

Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, 21231, United States; Recruiting

Arlene A. Forastiere, MD 410-955-9818 af@jhmi.edu

Massachusetts
Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States; Recruiting

Michael Benjamin Atkins, MD 617-667-1930

Tufts - New England Medical Center, Boston, Massachusetts, 02111, United States; Recruiting

John K. Erban, MD 617-636-5147 jerban@tufts-nemc.org

Michigan
CCOP - Kalamazoo, Kalamazoo, Michigan, 49007-3731, United States; Recruiting

Raymond Sterling Lord, MD 269-373-7488 rlord@wmcc.org

CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan, 48106, United States; Recruiting

Philip J. Stella, MD 877-590-5995

Minnesota
CCOP - Duluth, Duluth, Minnesota, 55805, United States; Recruiting

Robert J. Dalton, MD 218-786-8364 rdalton@smdc.org

CCOP - Metro-Minnesota, Saint Louis Park, Minnesota, 55416, United States; Recruiting

Patrick J. Flynn, MD 952-993-1517 patrick.flynn@usoncology.com

Mayo Clinic Cancer Center, Rochester, Minnesota, 55905, United States; Recruiting

Thomas M. Habermann, MD 507-284-2511

University of Minnesota Cancer Center, Minneapolis, Minnesota, 55455, United States; Recruiting

George L. Adams, MD 612-625-2410 adams002@umn.edu

Veterans Affairs Medical Center - Minneapolis, Minneapolis, Minnesota, 55417-2399, United States; Recruiting

Markus Gapany, MD 612-725-2000 ext. 3459 gapan001@maroon.tc.umn.edu

Nebraska
CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska, 68106, United States; Recruiting

James A. Mailliard, MD 402-280-4364 jamailliard@mrcc.cc

Midlands Cancer Center at Midlands Community Hospital, Papillion, Nebraska, 68128-4157, United States; Recruiting

James A. Mailliard, MD 402-593-3000

Veterans Affairs Medical Center - Omaha, Omaha, Nebraska, 68105, United States; Recruiting

James A. Mailliard, MD 402-280-5274

Nevada
CCOP - Southern Nevada Cancer Research Foundation, Las Vegas, Nevada, 89106, United States; Recruiting

John Allan Ellerton, MD, CM 702-384-0013 k.vavwagenen@sncrf.com

New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, 03756-0002, United States; Recruiting

Camilo E. Fadul, MD 603-650-6312 Camilo.e.fadul@dartmouth.edu

New Jersey
Cancer Institute of New Jersey, New Brunswick, New Jersey, 08903, United States; Recruiting

Joseph Aisner, MD 732-235-7401 aisnerjo@umdnj.edu

CCOP - Northern New Jersey, Hackensack, New Jersey, 07601, United States; Recruiting

Richard J. Rosenbluth, MD 201-996-5917

Veterans Affairs Medical Center - East Orange, East Orange, New Jersey, 07019, United States; Recruiting

Basil S. Kasimis, MD, DSc 973-676-1000 ext. 1544 Basil.Kasimis@med.va.gov

New Mexico
MBCCOP - University of New Mexico HSC, Albuquerque, New Mexico, 87131, United States; Recruiting

Cynthia K. Cathcart, MD 505-272-5688

New York
Albert Einstein Clinical Cancer Center, Bronx, New York, 10461, United States; Recruiting

Joseph A. Sparano, MD 718-904-2555 jsparano@montefiore.org

MBCCOP-Our Lady of Mercy Cancer Center, Bronx, New York, 10466, United States; Recruiting

Peter H. Wiernik, MD 718-920-1100

NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York, 10016, United States; Recruiting

Howard S. Hochster, MD 212-652-1912 howard.hochster@med.nyu.edu

Veterans Affairs Medical Center - Brooklyn, Brooklyn, New York, 11209, United States; Recruiting

Andrea Nadine Wiesel Leaf, MD 718-630-3691

Veterans Affairs Medical Center - New York, New York, New York, 10010, United States; Recruiting

Howard S. Hochster, MD 212-652-1912 howard.hochster@med.nyu.edu

North Dakota
CCOP - Merit Care Hospital, Fargo, North Dakota, 58122, United States; Recruiting

Preston D. Steen, MD 701-234-6161

Ohio
CCOP - Columbus, Columbus, Ohio, 43206, United States; Recruiting

J. Philip Kuebler, MD, PhD 614-443-2267

CCOP - Toledo Community Hospital, Toledo, Ohio, 43623-3456, United States; Recruiting

Paul L. Schaefer, MD 419-843-6147

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, 44195, United States; Recruiting

Robert Dreicer, MD, FACP 216-445-4623

MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland, Ohio, 44109, United States; Recruiting

Edward G. Mansour, MD 216-778-4394 emansour@metrohealth.org

Oklahoma
CCOP - Oklahoma, Tulsa, Oklahoma, 74136, United States; Recruiting

James B. Lockhart, MD 918-491-5878

Pennsylvania
Abramson Cancer Center at University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, United States; Recruiting

Daniel G. Haller, MD 215-662-6318

CCOP - Geisinger Clinic and Medical Center, Danville, Pennsylvania, 17822-2001, United States; Recruiting

Suresh G. Nair, MD 570-271-6413

CCOP - MainLine Health, Wynnewood, Pennsylvania, 19096, United States; Recruiting

Paul B. Gilman, MD 610-645-2057

Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111-2497, United States; Recruiting

Lori J. Goldstein, MD 215-728-2689 lj_goldstein@fccc.edu

Hahnemann University Hospital, Philadelphia, Pennsylvania, 19102-1192, United States; Recruiting

Pamela Ann Crilley, DO 215-762-8547

Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, 15236, United States; Recruiting

John Munn Kirkwood, MD 412-692-4724

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033-0850, United States; Recruiting

Witold Boleslaw Rybka, MD, FRCPC 717-531-1050 wrybka@med.hmc.psu.edu

Veterans Affairs Medical Center - Pittsburgh, Pittsburgh, Pennsylvania, 15240, United States; Recruiting

Timothy Carlos, MD 412-688-6248 timothy.carlos@med.va.gov

South Dakota
CCOP - Sioux Community Cancer Consortium, Sioux Falls, South Dakota, 57104, United States; Recruiting

Loren K. Tschetter, MD 605-328-8044 cincod@siouxvalley.org

Tennessee
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville, Tennessee, 37232-6307, United States; Recruiting

David Horton Johnson, MD 615-343-9454 david.h.johnson@vanderbilt.edu

Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville, Tennessee, 37212-2637, United States; Recruiting

Kenneth R. Hande, MD 615-327-4751

Texas
CCOP - Scott and White Hospital, Temple, Texas, 76508, United States; Recruiting

Lucas Wong, MD 254-724-7048 lwong@swmail.sw.org

Wisconsin
CCOP - Marshfield Clinic Research Foundation, Marshfield, Wisconsin, 54449, United States; Recruiting

Tarit Kumar Banerjee, MD, FACP 715-387-5134

CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay, Wisconsin, 54307-3453, United States; Recruiting

Gerald K. Bayer, MD 920-433-8889

Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin, 53226-3596, United States; Recruiting

David H. Vesole, MD, PhD 414-805-4646 dvesole@bmt.mcw.edu

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, 53792-0001, United States; Recruiting

James A. Stewart, MD 608-265-8131 stewart@biostat.wisc.edu

Veterans Affairs Medical Center - Madison, Madison, Wisconsin, 53705, United States; Recruiting

Mark R. Albertini, MD 608-262-7017

Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee, Wisconsin, 53295, United States; Recruiting

Mohammed A. Raheem, MD 414-384-2000

*** POSTED May 2004 ***