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

Conditions: on-small cell lung carcinoma in patients with predominantly non-squamous cell carcinoma histology
MedDRA version: 9.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrent
MedDRA version: 9.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastatic
MedDRA version: 9.1Level: PTClassification code 10061873Term: Non-small cell lung cancer

Registration Number: EUCTR2008-006914-62-HU

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 two but not more than three prior treatment regimens for NSCLC
o Prior therapy with bevacizumab (Avastin) permitted
o Prior therapy with standard EGFR inhibitors permitted. Every attempt should
be made to enroll patient who have received an EGFR inhibitor in the
geographic areas where this type of treatment is available.
•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, the subject is clinically stable
for at least 2 months prior to randomization. (Prior and ongoing corticosteroid
treatment is allowed, provided the dose is not high, stable and no dose
adjustments are needed after randomization).
•Male or female subjects = 18 years of age (= 20 for Japan) at the time of Informed
Consent
•Life expectancy of at least 12 weeks
•Ability to swallow oral medication
•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, MDRD
formula. (Measured creatinine clearance using EDTA, Inulin or 24 hours
urine methods is recommended for patients with equivocal results or low
body weight)

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]
•History of HIV infection or chronic 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
•Previous 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.
•Substance abuse, medical, psychological or social conditions that may interfere
with the subject’s participation in the study or evaluation of the study results
•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].
•Any disease which could affect the evaluation of the study drug
•Any condition that is unstable or could jeopardize the safety of the subject and
their compliance in the study
•Any condition which could affect the absorption or pharmacokinetics of the study
drug including any type of gastrointestinal resection or surgery

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 two or 3 prior treatment regimens.<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