A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY 43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

A randomized controlled trial comparing safety and efficacy of carboplatin and paclitaxel plus or minus sorafenib in chemonaive patients with stage III-IV non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small Cell Lung
• Intervention / Treatment: Drug: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel; Drug: Carboplatin plus Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 926
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal-Buenos Aires, Argentina, C1426ANZ
  • Santa Fé, Argentina, S3000FFV
  • Buenos Aires
    • El Palomar - Morón, Buenos Aires, Argentina, 1684
    • La Plata, Buenos Aires, Argentina, B1900AVG
    • Mar del Plata, Buenos Aires, Argentina, B7602CBM
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1405DCS
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
• Australia
  • New South Wales
    • Port Macquarie, New South Wales, Australia, 2444
    • Wollongong, New South Wales, Australia, 2500
  • Queensland
    • Brisbane, Queensland, Australia, 4029
  • South Australia
    • Adelaide, South Australia, Australia, 5065
  • Victoria
    • Frankston, Victoria, Australia, 3199
    • Melbourne, Victoria, Australia, 3144
  • Western Australia
    • Perth, Western Australia, Australia, 6000
• Belgium
  • Bruxelles - Brussel, Belgium, 1200
  • Charleroi, Belgium, 6000
  • La Louviere, Belgium, 7100
  • Liege, Belgium, 4000
• Brazil
  • Belo Horizonte, Brazil, 30380490
  • Bahia
    • Salvador, Bahia, Brazil, 40050410
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-230
    • Fortaleza, Ceará, Brazil, 60336-550
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil, 70390907
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-180
  • Minas Gerais
    • Nova Lima, Minas Gerais, Brazil, 34000000
  • Parana
    • Curitiba, Parana, Brazil, 80730-180
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90619900
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202-050
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784400
    • Jaú, Sao Paulo, Brazil, 17210-120
    • Ribeirao Preto, Sao Paulo, Brazil, 14015-140
    • Santo Andre, Sao Paulo, Brazil, 09090-780
    • Sorocaba, Sao Paulo, Brazil, 18030-510
    • São Paulo, Sao Paulo, Brazil
    • São Paulo, Sao Paulo, Brazil, 04024-002
    • São Paulo, Sao Paulo, Brazil, 01331010
    • São Paulo, Sao Paulo, Brazil, 05403-000
• Canada
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7L 2L7
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
    • Brampton, Ontario, Canada, L6W 3X4
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
• Chile
  • Santiago, Chile
  • Santiago, Chile, 760 0448
  • Santiago, Chile, 836-0156
  • Santiago, Chile, 838-0455
• France
  • Bobigny Cedex, France, 93009
  • Caen, France, 14073
  • Clamart, France, 92140
  • Metz, France, 57000
  • Nancy, France, 54100
  • Nice Cedex 2, France, 06102
  • Strasbourg, France, 67100
• Germany
  • Berlin, Germany, 12200
  • Hamburg, Germany, 21075
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
    • Mannheim, Baden-Württemberg, Germany, 68167
  • Bayern
    • Gauting, Bayern, Germany, 82131
    • München, Bayern, Germany, 80336
  • Hessen
    • Hofheim, Hessen, Germany, 65719
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
    • Hannover, Niedersachsen, Germany, 30625
    • Oldenburg, Niedersachsen, Germany, 26121
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
    • Essen, Nordrhein-Westfalen, Germany, 45136
    • Hemer, Nordrhein-Westfalen, Germany, 58675
    • Leverkusen, Nordrhein-Westfalen, Germany, 51375
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
• Hong Kong
  • Hong Kong, Hong Kong
• Hungary
  • Budapest, Hungary, 1529
  • Deszk, Hungary, 6772
  • Gyula, Hungary, 5703
  • Matrahaza, Hungary, 3233
  • Torokbalint, Hungary, 2045
• Italy
  • Bergamo, Italy, 24128
  • Genova, Italy, 16132
  • Milano, Italy, 20162
  • Parma, Italy, 43100
  • Pavia, Italy, 27100
  • Perugia, Italy, 06156
  • Roma, Italy, 00152
  • Torino, Italy, 10126
  • Torino
    • Orbassano, Torino, Italy, 10043
• Korea, Republic of
  • Seoul, Korea, Republic of, 138736
  • Seoul, Korea, Republic of, 135710
  • Seoul, Korea, Republic of, 110-799
• Netherlands
  • Zwolle, Netherlands, 8011 JW
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
• Poland
  • Gdansk, Poland, 80-952
  • Krakow, Poland, 31-115
  • Olsztyn, Poland, 10-228
  • Otwock, Poland, 05-400
  • Warszawa, Poland, 02-781
  • Warszawa, Poland, 04-141
  • Wroclaw, Poland, 53-439
• Puerto Rico
  • San Juan, Puerto Rico, 00921
• Russian Federation
  • Moscow, Russian Federation, 115478
  • Moscow, Russian Federation, 143423
  • Moscow, Russian Federation, 117837
  • St. Petersburg, Russian Federation, 198255
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28006
  • Madrid, Spain, 28034
  • Pontevedra, Spain, 36001
  • Zamora, Spain, 49021
  • Alicante
    • Elche, Alicante, Spain, 03202
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
• Sweden
  • Gävle, Sweden, 801 87
  • Stockholm, Sweden, 171 76
  • Uppsala, Sweden, 751 85
• Taiwan
  • Taichung, Taiwan, 40705
  • Taipei, Taiwan, 110
  • Taoyuan, Taiwan, 333
• United Kingdom
  • London, United Kingdom, SE1 9RT
  • Manchester, United Kingdom, M23 9LT
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
  • Dorset
    • Bornemouth, Dorset, United Kingdom, BH7 7DW
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Tucson, Arizona, United States, 85715
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
    • Springdale, Arkansas, United States, 72764
  • California
    • Anaheim, California, United States, 92801
    • Beverly Hills, California, United States, 90211-1850
    • Burbank, California, United States, 91595
    • Corona, California, United States, 92829
    • Encinitas, California, United States, 92024
    • Highland, California, United States, 92346
    • Los Angeles, California, United States, 90057
    • Orange, California, United States, 92868
    • Sacramento, California, United States, 95817
  • Colorado
    • Denver, Colorado, United States, 80218
  • Florida
    • Lakeland, Florida, United States, 33805
    • Merritt Island, Florida, United States, 32952
    • Orlando, Florida, United States, 32806
    • Orlando, Florida, United States, 32804
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Marietta, Georgia, United States, 30060
    • Savannah, Georgia, United States, 31405
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Skokie, Illinois, United States, 60076
    • Skokie, Illinois, United States, 60077
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
    • Indianapolis, Indiana, United States, 46260
    • Indianapolis, Indiana, United States, 46202
    • Indianapolis, Indiana, United States, 46254
    • Kokomo, Indiana, United States, 46902
  • Iowa
    • Sioux City, Iowa, United States, 51101
  • Kansas
    • Hutchinson, Kansas, United States, 67502
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Louisville, Kentucky, United States, 40215
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
    • Metairie, Louisiana, United States, 70006
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
    • Pittsfield, Massachusetts, United States, 01201
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
    • Detroit, Michigan, United States, 48202
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
  • Missouri
    • Jefferson City, Missouri, United States, 65109
    • Kansas City, Missouri, United States, 64111
    • Kansas City, Missouri, United States, 64131
    • St. Louis, Missouri, United States, 63141
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States, 89106
    • Las Vegas, Nevada, United States, 89102
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
    • Morristown, New Jersey, United States, 07962-1089
  • New York
    • New York, New York, United States, 10029
    • Rochester, New York, United States, 14622
    • Staten Island, New York, United States, 10305
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
    • Fargo, North Dakota, United States, 58122
  • Ohio
    • Columbus, Ohio, United States, 43213
    • Columbus, Ohio, United States, 43235
    • Dayton, Ohio, United States, 45429
    • Dover, Ohio, United States, 44622
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
    • Tulsa, Oklahoma, United States, 74136
  • Oregon
    • Portland, Oregon, United States, 97213
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
    • Bethlehem, Pennsylvania, United States, 18015
    • Philadelphia, Pennsylvania, United States, 19115
    • Pottsville, Pennsylvania, United States, 17901
    • Sayre, Pennsylvania, United States, 18840
  • South Carolina
    • Charleston, South Carolina, United States, 29403
    • Greenville, South Carolina, United States, 29615
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
    • Nashville, Tennessee, United States, 37232-6307
  • Texas
    • Trophy Club, Texas, United States, 76262
  • Utah
    • Salt Lake City, Utah, United States, 84112
  • Virginia
    • Abingdon, Virginia, United States, 24211
    • Fairfax, Virginia, United States, 22031
    • Richlands, Virginia, United States, 24641
    • Richmond, Virginia, United States, 23230
    • Richmond, Virginia, United States, 23298-0037
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage IIIB (with effusion) or Stage IV NSCLC any histology
• No prior chemotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Greater than or equal to 18 years of age
• Life expectancy at least 12 weeks
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Prior systemic anti cancer therapy
• Known brain metastasis. Patients with neurological symptoms should undergo at computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
• Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug
• Thrombotic or embolic events including Transient ischemic attack (TIA) within the past 6 months
• Uncontrolled hypertension
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Major surgery within 4 weeks
• Evidence or history of bleeding diathesis or coagulopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib + C/P; Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), [400 mg orally, twice daily] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.	Drug: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel; Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), [400 mg orally, twice daily] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.
Active Comparator: Placebo + C/P; Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.	Drug: Carboplatin plus Paclitaxel; Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo	Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks during study treatment and every 3 months during post-treatment.	Outcome measure was assessed every 3 weeks starting from randomization, during treatment period and every 3 months during follow-up period until death was recorded or up to data cutoff (1Oct2007) used for planned formal interim analysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS determined as time (days) from the date of randomization at start of study to disease progression (radiological or clinical) or death due to any cause, if death occurs before progression.	Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis
Overall Best Response	Best overall tumor response for the ITT population was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased).	Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis
Duration of Response	Duration of response (PR or better) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented).	Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis
Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT)	Functional Assessment of Cancer Therapy - Lung cancer subscore (FACT-L). Patient reported outcome as assessed by FACT-L score. FACT-L questionnaire comprises statements about physical, social / family, emotional and functional well-being as well as additional concerns which have to be rated by the patients (0="not at all" to 4="very much"). Cycle duration defined as 21 days. Change from baseline in Total FACT-L on day 1 of cycles 3,5,7,9 (weeks 7,13,19 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation.	Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every other cycle (i.e. Cycle 3, 5, 7 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis
Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT)	Lung Cancer Symptoms (LCS) subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). Cycle duration defined as 21 days. Change from baseline in LCS Subscale on day 1 of cycles 2 through 9 (weeks 4,7,10,13,16,19,22 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation.	Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every cycle (i.e. Cycle 2, 3, 4, 5 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Scagliotti G, Novello S, von Pawel J, Reck M, Pereira JR, Thomas M, Abrao Miziara JE, Balint B, De Marinis F, Keller A, Aren O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, Dimatteo S, Hanna N. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010 Apr 10;28(11):1835-42. doi: 10.1200/JCO.2009.26.1321. Epub 2010 Mar 8.

Helpful Links

• Click here and search for information of Bayer products for Europe

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: March 8, 2006
• First Submitted That Met QC Criteria: March 8, 2006
• First Posted (Estimate): March 10, 2006

Study Record Updates

• Last Update Posted (Estimate): November 4, 2014
• Last Update Submitted That Met QC Criteria: October 28, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Sorafenib; Albumin-Bound Paclitaxel
• Other Study ID Numbers: 11961; 2005-005245-19 (EudraCT Number)