A Randomized Phase III Trial of Carboplatin, Paclitaxel and Thoracic Radiotherapy, With or Without Thalidomide, in Patients With Stage III Non-Small Cell Lung Cancer (NSCLC)
A Randomized Phase III Trial of Carboplatin, Paclitaxel and Thoracic Radiotherapy, With or Without Thalidomide, in Patients With Stage III Non-Small Cell Lung Cancer (NSCLC)
This randomized phase III trial is studying carboplatin, paclitaxel, radiation therapy, and thalidomide to see how well they work compared to carboplatin, paclitaxel, and radiation therapy alone in treating patients with newly diagnosed stage III non-small cell lung cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of non-small cell lung cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without thalidomide.
OBJECTIVES:
I. Compare the survival and time to progression of patients with stage IIIA or IIIB non-small cell lung cancer when treated with carboplatin, paclitaxel, and chemoradiotherapy with or without thalidomide.
II. Evaluate the toxicity of the thalidomide-containing regimen and compare response rates of the two groups.
III. Determine whether the inactivation of p16, Death-associated protein kinase (DAP-kinase), O6-methylguanine-DNA methyltransferase (MGMT) gene, or tissue-inhibitor of metalloproteinase 3 (TIMP-3) genes can be used to predict survival in these patients treated with this regimen.
IV. Determine whether the detection of a methylation biomarker in serum can be used to predict survival in these patients treated with this regimen.
OUTLINE: This is a randomized study. Patients are stratified according to disease histology (squamous vs nonsquamous), performance status (0 vs 1), disease stage (IIIA vs IIIB), and time of randomization (before addition of chemoradiotherapy vs after). Patients are randomized to one of two treatment arms.
ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours immediately followed by carboplatin IV over 15-30 minutes on days 1 and 22. Treatment continues every 22 days in the absence of unacceptable toxicity or disease progression.
ARM B: Patients receive paclitaxel and carboplatin as in arm A. Patients also receive oral thalidomide and oral low-dose aspirin daily beginning on day 1 for up to 24 months in the absence of disease progression.
Beginning between days 43-50, patients in both arms with stable or responding disease receive chemoradiotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 15-30 minutes once weekly for 6 weeks and radiotherapy (RT) 5 days a week for 6 weeks. Arm B patients continue oral thalidomide.
Patients are followed every 2 months for 2 years and then every 6 months for 3 years.
Inclusion Criteria:
Histologically confirmed newly diagnosed non-small cell bronchogenic carcinoma
Unresectable stage IIIA
OR
Stage IIIB disease without significant pleural effusion
Bidimensionally measurable or evaluable disease
18 and over
ECOG performance status 0-1
Adequate hematopoietic, hepatic, and renal function obtained <=4 weeks prior to registration:
Fertile patients must use 2 methods of effective contraception for 4 weeks prior to, during, and for 4 weeks after study therapy
Concurrent filgrastim (G-CSF) allowed for persistent neutropenia
Exclusion Criteria:
Fort Smith, Arkansas 72903, United States
Stanford, California 94305, United States
Grand Junction, Colorado 81502, United States
Savannah, Georgia 31403-3089, United States
Valdosta, Georgia 31603, United States
Chicago, Illinois 60611-3013, United States
Skokie, Illinois 60076, United States
La Porte, Indiana 46350, United States
Des Moines, Iowa 50309, United States
Des Moines, Iowa 50314, United States
West Des Moines, Iowa 50266, United States
Madisonville, Kentucky 42431, United States
Springfield, Massachusetts 01199, United States
Ann Arbor, Michigan 48106-0995, United States
Dearborn, Michigan 48123-2500, United States
Grosse Pointe Woods, Michigan 48236, United States
Kalamazooaa, Michigan 49001, United States
Saint Joseph, Michigan 49085, United States
Lichfield, Minnesota 55355, United States
Minneapolis, Minnesota 55407, United States
Robbinsdale, Minnesota 55422-2900, United States
Flemington, New Jersey 08822, United States
Marlton, New Jersey 08053, United States
Morristown, New Jersey 07962, United States
New Brunswick, New Jersey 08903, United States
Voorhees Township, New Jersey 08043, United States
Rochester, New York 14621, United States
The Bronx, New York 10461, United States
The Bronx, New York 10466, United States
Allentown, Pennsylvania 18105, United States
DuBois, Pennsylvania 15801, United States
Harrisburg, Pennsylvania 17105, United States
Hershey, Pennsylvania 17033-0850, United States
Pittsburgh, Pennsylvania 15232, United States
Wilkes-Barre, Pennsylvania 18711, United States
Aiken, South Carolina 29801, United States
Sioux Falls, South Dakota 57117-5039, United States
Kingsport, Tennessee 37662, United States
Charlottesville, Virginia 22908, United States
Charleston, West Virginia 25304, United States
La Crosse, Wisconsin 54601, United States