E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung carcinoma in patients with predominantly non-squamous cell carcinoma histology |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029515 |
E.1.2 | Term | Non-small cell lung cancer recurrent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
The primary efficacy variable is overall survival (OS). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: o Haemoglobin > 9.0 g/dl o Absolute neutrophil count (ANC) >1,500/mm3 o Platelet count ≥ 100,000/µl o Total bilirubin ≤ 1.5 x the upper limit of normal o ALT < 2.5 x upper limit of normal (≤ 5 x upper limit of normal in patients with liver metastases) o AST < 2.5 x upper limit of normal (≤ 5 x upper limit of normal in patients with liver metastases) o Alkaline phosphatase < 4 x upper limit of normal (≤ 5 x upper limit of normal in patients with liver metastases) o PT-INR or PTT < 1.5 x upper limit of normal o Serum creatinine < 1.5 x upper limit of normal o Calculated 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)
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E.4 | Principal 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: o Congestive heart failure >New York Heart Association (NYHA) class 2 o Active 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] o Cardiac arrhythmias (>Grade 2 NCI-CTCAE vers. 3.0) which are poorly controlled with anti-arrhythmic therapy o Uncontrolled 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is overall survival (OS). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study for regulatory purposes will be considered to be when the last subject has had their end of study visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |