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)

NCT ID: NCT00449033

Last Updated: 2015-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 904 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2011-06-30

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)

Detailed Description

During follow-up, it was determined that there was one additional patient on placebo that was still receiving treatment as of 06 APR 2010 and therefore 10 patients' data are reported in the current CSR addendum, 6 in the sorafenib + GC group and 4 in the placebo + GC group, and as before all in the ITT (non-squamous) population.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sorafenib (Nexavar, BAY43-9006) + GC

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.

Group Type: EXPERIMENTAL

Sorafenib (Nexavar, BAY43-9006)

Intervention Type: 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

Gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Placebo + GC

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

Sorafenib (Nexavar, BAY43-9006)

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious, non-healing wound, ulcer, or bone fracture
• Uncorrected dehydration
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Known or suspected allergy to the investigational agent or any agent given in association with this trial
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
• Patients unable to swallow oral medications
• Any malabsorption condition
• Patients with a hearing impairment (FOR GERMANY ONLY)
• NSCLC patients with squamous cell carcinoma diagnosis documented either by cytology or biopsy.
• Excluded therapies and medications, previous and concomitant:

• Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for NSCLC
• Concomitant use of nephrotoxic drugs, ototoxic drugs, anticonvulsant, anti-gout treatment
• Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section)
• Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section) (FOR FRANCE ONLY)
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug (bronchoscopy is allowed)
• Granulocyte colony stimulating factor (GCSF) or Granulocyte macrophage colony stimulating factor (GMCSF), within 3 weeks of study entry (these growth factors may be used during the study thereafter).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Innsbruck, , Austria

Linz, , Austria

Vienna, , Austria

Vienna, , Austria

Brasschaat, , Belgium

Bruxelles - Brussel, , Belgium

Edegem, , Belgium

Leuven, , Belgium

Liège, , Belgium

Namur, , Belgium

Salvador, Estado de Bahia, Brazil

Salvador, Estado de Bahia, Brazil

Salvador, Estado de Bahia, Brazil

Brasília, Federal District, Brazil

Goiânia, Goiás, Brazil

Goiânia, Goiás, Brazil

Belo Horizonte, Minas Gerais, Brazil

Rio de Janeiro, Rio de Janeiro, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Jaú, São Paulo, Brazil

Santo André, São Paulo, Brazil

Santo André, São Paulo, Brazil

São Paulo, São Paulo, Brazil

São Paulo, São Paulo, Brazil

São Paulo, São Paulo, Brazil

São Paulo, São Paulo, Brazil

Sorocaba, São Paulo, Brazil

Montreal, Quebec, Canada

Guangzhou, Guangdong, China

Wuhan, Hubei, China

Nanjing, Jiangsu, China

Hangzhou, Zhejiang, China

Hangzhou, Zhejiang, China

Beijing, , China

Shanghai, , China

Shanghai, , China

Nicosia, , Cyprus

HUS, , Finland

Preitilä, , Finland

Tampere, , Finland

Bayonne, , France

Grenoble, , France

Grenoble, , France

Hyères, , France

Le Mans, , France

Marseille, , France

Nantes, , France

Nîmes, , France

Paris, , France

Perpignan, , France

Pierre-Bénite, , France

Strasbourg, , France

Tours, , France

Heidelberg, Baden-Wurttemberg, Germany

Karlsruhe, Baden-Wurttemberg, Germany

Löwenstein, Baden-Wurttemberg, Germany

Gauting, Bavaria, Germany

Hamburg, City state of Hamburg, Germany

Frankfurt am Main, Hesse, Germany

Hofheim, Hesse, Germany

Cologne, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Leipzig, Saxony, Germany

Großhansdorf, Schleswig-Holstein, Germany

Bad Berka, Thuringia, Germany

Heraklion, Crete, Greece

Athens, Greece, Greece

Athens, , Greece

Budapest, , Hungary

Budapest, , Hungary

Deszk, , Hungary

Mátraháza, , Hungary

Székesfehérvár, , Hungary

Törökbálint, , Hungary

Ashkelon, , Israel

Holon, , Israel

Kfar Saba, , Israel

Rehovot, , Israel

Tel Litwinsky, , Israel

Rozzano, Milano, Italy

Monza, Monza-Brianza, Italy

Aviano, Pordenone, Italy

Bologna, , Italy

Catania, , Italy

Florence, , Italy

Livorno, , Italy

Milan, , Italy

Roma, , Italy

Sassari, , Italy

Venezia, , Italy

Verona, , Italy

Guadalajara, Jalisco, Mexico

Mexico City, Mexico City, Mexico

Monterrey, Nuevo León, Mexico

's-Hertogenbosch, , Netherlands

Ede, , Netherlands

Harderwijk, , Netherlands

Heerlen, , Netherlands

Nieuwegein, , Netherlands

A Coruña, A Coruña, Spain

Barcelona, Barcelona, Spain

Terrassa, Barcelona, Spain

Cruces/Barakaldo, Bilbao, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Málaga, Málaga, Spain

Seville, Sevilla, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Basel, Canton of Basel-City, Switzerland

Bern, Canton of Bern, Switzerland

Genéve, Canton of Geneva, Switzerland

Cambridge, Cambridgeshire, United Kingdom

Aberdeen, Grampian, United Kingdom

Leicester, Leicestershire, United Kingdom

London, London, United Kingdom

London, London, United Kingdom

Sutton, Surrey, United Kingdom

Wolverhampton, West Midlands, United Kingdom

Birmingham, , United Kingdom

Countries

Austria; Belgium; Brazil; Canada; China; Cyprus; Finland; France; Germany; Greece; Hungary; Israel; Italy; Mexico; Netherlands; Spain; Switzerland; United Kingdom

References

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.

Reference Type: RESULT

PMID: 22851564 (View on PubMed)

Related Links

http://www.clinicaltrialsregister.eu

Click here and search for Bayer Product information provided by EMA

Other Identifiers

2006-002688-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12006

Identifier Type: -

Identifier Source: org_study_id