A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC)

NCT00449033 | Completed Phase 3 Results DMC

• 2 other identifiers: 120062006-002688-26
• Study Type: interventional
• Target: 904
• Locations: 18 countries
• Sites: 122

Brief Summary

Evaluation of gemcitabine and cisplatin in combination with either sorafenib or placebo for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small Cell Lung Cancer (NSCLC); Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) in the ITT (Non-squamous) Population

  Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.

  from randomization of the first patient until 38 months or date of death of any cause whichever came first

Secondary Outcomes (14)

• OS in the ITT (Both Squamous and Non-squamous) Population

  from randomization of the first patient until 38 months or date of death of any cause whichever came first

• OS in the ITT (Squamous) Population

  from randomization of the first patient until 38 months or date of death of any cause whichever came first

• Progression-free Survival (PFS) in the ITT (Non-squamous) Population

  from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

• Time to Progression (TTP) in the ITT (Non-squamous) Population

  from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

• Percentage of Participants With Different Tumor Response in the ITT (Non-squamous) Population

  from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks

Study Arms (2)

Sorafenib (Nexavar, BAY43-9006) + GC

EXPERIMENTAL

Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with sorafenib. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: sorafenib 2 tablets (200 mg) taken orally (po) twice daily (bid). If the patient had radiological evidence of stable disease (SD) or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which sorafenib was administered 400 mg bid until criteria for withdrawal were met.

Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Gemcitabine; Drug: Cisplatin

Placebo + GC

PLACEBO COMPARATOR

Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m\^2 infusion (IV), followed by cisplatin 75 mg/ m\^2 IV; Day 8: gemcitabine 1250 mg/ m\^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met.

Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Sorafenib (Nexavar, BAY43-9006) DRUG

Multikinase inhibitor, Sorafenib 400 mg po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m\^2 IV, Cisplatin 75 mg/m\^2 IV

Sorafenib (Nexavar, BAY43-9006) + GC

Placebo DRUG

Placebo 2 tablets po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m\^2 IV, Cisplatin 75 mg/m\^2 IV

Placebo + GC

Gemcitabine DRUG

Chemotherapy component; Gemcitabine 1250 mg/m\^2 IV

Placebo + GC; Sorafenib (Nexavar, BAY43-9006) + GC

Cisplatin DRUG

Chemotherapy component; Cisplatin 75 mg/m\^2 IV

Placebo + GC; Sorafenib (Nexavar, BAY43-9006) + GC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years old
• Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC of non-squamous cell carcinoma subtype. (thoracentesis or pericardiocentesis is not necessary if a biopsy of the original tumor is available to confirm diagnosis of NSCLC).
• Patients with at least one measurable lesion. Lesions must be measured by CT-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix 10.3)
• Life expectancy of at least 12 weeks
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
• Hemoglobin \>/= 9.0 g/dl (\>/= 5.6 mmol/l)
• Absolute neutrophil count (ANC) \>/= 1,500/mm3
• Platelet count \>/= 100,000/µl
• Total bilirubin \</= 1.5 x upper limit of normal
• Alanine transaminase (ALT) and Aspartate transaminase (AST) \</= 2.5 x upper limit of normal (\</= 5 x upper limit of normal for patients with liver involvement of their cancer)
• Alkaline Phosphatase \</= 4 x upper limit of normal
• PT-INR (Prothrombin Time - International Normalized Ratio) (international normalized ratio of PT) /PTT (Partial Thromboplastin Time) \< 1.5 x upper limit of normal
• Serum Creatinine \</= 1.5 times the upper limit of normal and Serum Creatinine Clearance \>/= 70ml/min
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

You may not qualify if:

• Excluded medical conditions:
• Cardiac disease: Congestive heart failure \> class II NYHA (New York Heart Association). Patients must not have unstable angina (anginal symptoms at rest) or active coronary artery disease (CAD), or myocardial infarction within the past 6 months
• Cardiac arrhythmias requiring anti-arrhythmic therapy
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• History of HIV (Human immunodeficiency virus) infection or chronic hepatitis B or C
• Active clinically serious infections (\> grade 2 NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0)
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis.
• History of organ allograft
• Patients with evidence or history of bleeding diathesis or coagulopathy
• Patients undergoing renal dialysis
• Cancer other than NSCLC within 5 years prior to start of study treatment EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumors \[Ta (Noninvasive tumor), Tis (Carcinoma in situ) \& T1 (Tumor invades lamina propria)\]
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug

Sponsors & Collaborators

• Bayer: lead

Study Sites (122)

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Innsbruck, 6020, Austria

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Linz, 4010, Austria

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Vienna, 1130, Austria

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Vienna, 1140, Austria

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Brasschaat, 2930, Belgium

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Bruxelles - Brussel, 1200, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Namur, 5000, Belgium

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Salvador, Estado de Bahia, 40050410, Brazil

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Salvador, Estado de Bahia, 40170-070, Brazil

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Salvador, Estado de Bahia, 41820 021, Brazil

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Brasília, Federal District, 70840 901, Brazil

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Goiânia, Goiás, 74075040, Brazil

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Goiânia, Goiás, 74605-070, Brazil

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Belo Horizonte, Minas Gerais, 30110-090, Brazil

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Rio de Janeiro, Rio de Janeiro, 20231 050, Brazil

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Porto Alegre, Rio Grande do Sul, 90050 170, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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Jaú, São Paulo, 17210-120, Brazil

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Santo André, São Paulo, 09060-870, Brazil

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Santo André, São Paulo, 09090-780, Brazil

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São Paulo, São Paulo, 01221020, Brazil

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São Paulo, São Paulo, 01331020, Brazil

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São Paulo, São Paulo, 05403-010, Brazil

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São Paulo, São Paulo, 05651-901, Brazil

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Sorocaba, São Paulo, 18030-510, Brazil

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Montreal, Quebec, H3A 1A1, Canada

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Guangzhou, Guangdong, 510060, China

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Wuhan, Hubei, 430030, China

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Nanjing, Jiangsu, 210002, China

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Hangzhou, Zhejiang, 310016, China

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Hangzhou, Zhejiang, 310022, China

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Beijing, 100021, China

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Shanghai, 200030, China

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Shanghai, 200433, China

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Nicosia, 2006, Cyprus

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HUS, 00029, Finland

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Preitilä, 21540, Finland

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Tampere, FIN-33521, Finland

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Bayonne, 64100, France

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Grenoble, 38043, France

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Grenoble, 38100, France

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Hyères, 83400, France

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Le Mans, 72015, France

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Marseille, 13275, France

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Nantes, 44805, France

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Nîmes, 30907, France

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Paris, 75908, France

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Perpignan, 66000, France

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Pierre-Bénite, 69495, France

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Strasbourg, 67901, France

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Tours, 37044, France

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Heidelberg, Baden-Wurttemberg, 69126, Germany

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Karlsruhe, Baden-Wurttemberg, 76137, Germany

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Löwenstein, Baden-Wurttemberg, 74245, Germany

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Gauting, Bavaria, 82131, Germany

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Hamburg, Hamburg, 21075, Germany

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Frankfurt am Main, Hesse, 60431, Germany

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Hofheim, Hesse, 65719, Germany

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Cologne, North Rhine-Westphalia, 51109, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Leipzig, Saxony, 04207, Germany

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Großhansdorf, Schleswig-Holstein, 22927, Germany

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Bad Berka, Thuringia, 99437, Germany

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Heraklion, Crete, 711 10, Greece

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Athens, Greece, 11527, Greece

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Athens, 11527, Greece

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Budapest, 1121, Hungary

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Budapest, 1125, Hungary

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Deszk, 6772, Hungary

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Mátraháza, 3233, Hungary

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Székesfehérvár, 8000, Hungary

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Törökbálint, 2045, Hungary

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Ashkelon, 7830604, Israel

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Holon, 58100, Israel

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Kfar Saba, 4428164, Israel

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Rehovot, 7610001, Israel

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Tel Litwinsky, 5262000, Israel

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Rozzano, Milano, 20089, Italy

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Monza, Monza-Brianza, 20052, Italy

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Aviano, Pordenone, 33081, Italy

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Bologna, 40138, Italy

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Catania, 95122, Italy

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Florence, 50134, Italy

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Livorno, 57124, Italy

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Milan, 20132, Italy

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Roma, 00152, Italy

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Sassari, 07100, Italy

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Venezia, 30122, Italy

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Verona, 37134, Italy

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Guadalajara, Jalisco, 44280, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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's-Hertogenbosch, 5211 RW, Netherlands

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Ede, 6716 RP, Netherlands

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Harderwijk, 3844 DG, Netherlands

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Heerlen, 6419 PC, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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A Coruña, A Coruña, 15006, Spain

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Barcelona, Barcelona, 08025, Spain

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Terrassa, Barcelona, 08227, Spain

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Cruces/Barakaldo, Bilbao, 48903, Spain

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Madrid, Madrid, 28040, Spain

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Madrid, Madrid, 28041, Spain

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Málaga, Málaga, 29010, Spain

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Seville, Sevilla, 41013, Spain

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Valencia, Valencia, 46010, Spain

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Valencia, Valencia, 46014, Spain

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Valencia, Valencia, 46015, Spain

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Basel, Canton of Basel-City, 4031, Switzerland

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Bern, Canton of Bern, 3010, Switzerland

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Genéve, Canton of Geneva, 1205, Switzerland

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Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

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Aberdeen, Grampian, AB25 2ZN, United Kingdom

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Leicester, Leicestershire, LE1 5WW, United Kingdom

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London, London, SE1 9RT, United Kingdom

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London, London, SW3 6JJ, United Kingdom

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Sutton, Surrey, SM2 5PT, United Kingdom

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Wolverhampton, West Midlands, WV10 0QP, United Kingdom

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Birmingham, B15 2TH, United Kingdom

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Related Publications (1)

• Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, Zhang L, Liao M, Sun Y, Gans S, Syrigos K, Le Marie E, Gottfried M, Vansteenkiste J, Alberola V, Strauss UP, Montegriffo E, Ong TJ, Santoro A; NSCLC [non-small-cell lung cancer] Research Experience Utilizing Sorafenib (NExUS) Investigators Study Group. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012 Sep 1;30(25):3084-92. doi: 10.1200/JCO.2011.39.7646. Epub 2012 Jul 30.

  PMID: 22851564 RESULT

Related Links

• Click here and search for Bayer Product information provided by EMA

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Sorafenib; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

Inclusion of squamous patients stopped in FEB 2008, as 11961 (NCT00558636) trial reported higher mortality for this subgroup. Squamous patients in 12006 (NCT00449033) trial discontinued drug as a precaution endorsed by Data Monitoring Committee.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer HealthCare AG

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2007
• First Posted: March 19, 2007
• Study Start: February 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2011
• Last Updated: April 23, 2015
• Results First Posted: September 9, 2011

Record last verified: 2015-04

Locations

NL (5); IT (12); AU (4); CN (8); HU (6); GR (3); ES (11); BR (18); IL (5); CH (3); FI (3); CA (1); DE (12); BE (6); CY (1); FR (13); ME (3); GB (8)