A Phase III, multi-center, placebo–controlled trial of Sorafenib (BAY 43-9006) in patients with relapsed or refractory advanced predominantly non squamous Non-Small Cell Lung Cancer (NSCLC) after 2 or 3 previous treatment regimens for advanced disease

Conditions: on-small cell lung carcinoma in patients with predominantly non-squamous cell carcinoma histology
MedDRA version: 13.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 13.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 13.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2008-006914-62-GR

Lead Sponsor: Bayer HealthCare AG, 51368 Leverkusen, Germany

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 700

Inclusion Criteria

Inclusion criteria must be met at the time of screening unless otherwise specified.
•Ability to understand and willingness to sign a written Informed Consent. A signed Informed Consent must be obtained prior to performing any study specific procedures.
•Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically (documentation of original cytology/ biopsy result is acceptable).
•Patients must have measurable or non-measurable disease as defined in Section 4.6.4.2. All sites of disease must be evaluated within 4 weeks prior to first dose of study medication.
•At least 2 but not more than 3 prior treatment regimens for advanced NSCLC (Adjuvant or new-adjuvant anti-cancer treatments after which a relapse occurred within 1 year of therapy will be counted. Maintenance anti-cnacer tretment is counted as a separate regimen, if it was not administered as part of the immediate- past regimen)
- prior therapy with bnecacizumab (Avastin) is permitted
- prior therapy with standard EGFR inhibitors is permitted
•ECOG Performance Status of 0 or 1
•History of metastatic brain or meningeal tumors allowed, provided definitive therapy (surgery and/or radiation) has been administered before randomization, no further treatment of brain metastases is planned, and the subject is clinically and radiologically stable for at least 2 months prior to randomization. (Patients must be asymptomatic and off steroid treatment for at least 14 days prior to study entry (i.e. signature date of Study Informed Consent Form). Discontinuation of corticosteroid treatment must be done independent of study participation as per local standard of care and consent procedures).
•Life expectancy of at least 12 weeks
•Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment (assessed centrally)
•Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and during the first 4 weeks after the completion of trial
•Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug:
oHaemoglobin > 9.0 g/dl
oAbsolute neutrophil count (ANC) >1,500/mm3
oPlatelet count = 100,000/µl
oTotal bilirubin = 1.5 x the upper limit of normal
oALT < 2.5 x upper limit of normal (= 5 x upper limit of normal in patients with liver metastases)
oAST < 2.5 x upper limit of normal (= 5 x upper limit of normal in patients with liver metastases)
oAlkaline phosphatase < 4 x upper limit of normal (= 5 x upper limit of normal in patients with liver metastases)
oPT-INR or PTT < 1.5 x upper limit of normal
oSerum creatinine < 1.5 x upper limit of normal
oCalculated creatinine clearance of = 50 mL/min e.g.Cockroft-Gault, (Measured creatinine clearance using EDTA, Inulin or 24 hours urine methods is recommended for patients with equivocal results or low body weight) NOTE: The central lab will use the Cockcroft-Gault calculation. Measured creatinine clearance will be done locally only if needed.
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

Patients who meet the following criteria at the time of screening will be excluded:
•NSCLC patients with predominantly squamous cell carcinoma histology
Excluded medical conditions:
•History of cardiac disease:
oCongestive heart failure >New York Heart Association (NYHA) class 2
oActive coronary artery disease (CAD), i.e. angina with onset in last 3 months or with symptoms at rest [myocardial infarction more than 6 months prior to study entry is allowed]
oCardiac arrhythmias (>Grade 2 NCI-CTCAE vers. 3.0) which are poorly controlled with anti-arrhythmic therapy
oUncontrolled hypertension [systolic blood pressure = 150 mmHg or diastolic blood pressure = 90 mmHg despite two anti-hypertensive medications]
•Any of the following:
- History of HIV infection
- Current chronic active or acute hepatitis B or C
•History of organ allograft
•Active clinically serious infections (> grade 2 NCI-CTCAE vers. 3.0)
•Patients with seizure disorder requiring medication (Patients who experienced seizures due to brain metastases prior to radical treatment of these metastases are allowed if the inclusion criterion related to brain metastases is adhered to - see section 4.2.1, inclusion criteria, for details).
•Patients with evidence or history of bleeding diathesis or coagulopathy
•Patients undergoing renal dialysis
•Pulmonary hemorrhage/ bleeding event = CTCAE grade 2 within four weeks prior to the first dose of the study drug
•Any other hemorrhage/ bleeding event = CTCAE grade 3 within four weeks prior to the first dose of the study drug
•Non-healing wound, ulcer or bone fracture
•Thrombotic or embolic venous or arterial events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months prior to the first dose of study drug
•Previously untreated or concurrent cancer that is distinct in primary site or histology from NSCLC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, T1). Any cancer curatively treated >3 years prior to entry is permitted. All treatments must be completed at least 3 years prior to study entry (i.e. signature date of Study Informed Consent).
•Known or suspected allergy or any other contraindication for sorafenib administration
•Pregnant or breast-feeding women. [Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and during the first four weeks after the completion of trial].

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this phase III study is to compare the efficacy and safety of sorafenib monotherapy plus best supportive care (BSC) versus placebo plus BSC for the treatment of patients with relapsed or refractory advanced predominantly non squamous NSCLC after 2 or 3 prior treatment regimens for advanced disease.<br><br>The primary efficacy variable is overall survival (OS).;Secondary Objective: Secondary efficacy variables are progression-free-survival (PFS), disease control rate (DCR), best overall response rate (ORR), time to progression (TTP), and patient reported outcomes (PRO) on health related quality of life (HRQOL), lung cancer symptoms and utilities. ;Primary end point(s): The primary efficacy variable is overall survival (OS).

Secondary Outcome Measures

Name	Time	Method