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) - NEXUS

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-002688-26-HU
• Date of registration: 05/06/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer Schering Pharma AG
• Public title: 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) - NEXUS
• Scientific title: 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) - NEXUS
• Date of first enrolment: 30/09/2008
• Target sample size: 1086
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002688-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, France, Germany, Greece, Hungary, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion 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 ³ 9.0 g/dl (³ 5.6 mmol/l)
• Absolute neutrophil count (ANC) ³ 1,500/mm3
• Platelet count ³ 100,000/?l
• Total bilirubin £ 1.5 x upper limit of normal
• ALT and 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 (international normalized ratio of PT) /PTT < 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.
• ECOG Performance Status of 0 or 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Cardiac disease: Congestive heart failure > class II NYHA. 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 > 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

First-line treatment of patients with stage IIIb with effusion and stage IV. non-small cell lung cancer (NSCLC)
MedDRA version: 9.1 Level: LLT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB
MedDRA version: 9.1 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV

Intervention(s)

Trade Name: Nexavar
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The objective of this phase III study is to compare the efficacy and safety of sorafenib in combination with gemcitabine and cisplatin versus placebo with gemcitabine and cisplatin for first-line treatment of patients with stage IIIB (with effusion) or Stage IV NSCLC.

The two primary efficacy objectives are to compare overall survival (OS) and progression-free-survival (PFS) in patients treated with gemcitabine, cisplatin and sorafenib to patients treated with gemcitabine, cisplatin and placebo.

Primary end point(s): The primary efficacy variables are overall survival (OS) and progression-free survival (PFS). One-sided alpha of 0.02 and 0.005 will be used for OS and PFS analyses respectively, so that the overall alpha for both primary end
points is 0.025 (one-sided).

Secondary Objective: Secondary efficacy objectives will include tumor responses and patient reported outcomes (PRO).

Secondary ID(s)

2006-002688-26-DE

not available

BAY 43-9006/12006