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 2 or 3 prior treatment regimens for advanced disease.
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 2 but not more than 3 prior standard 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. Maintainance anti-cancer treatment is counted as a seperate regimen, if it was not administered as part of the immediate-past regimen) - prior therapy with bevacizumab (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 ans 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 asper 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 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 (Measured creatinine clearance using EDTA, Inulin or 24hours urine methods is recommended for patients with equivocal results or low body weight). NOTE: The central lab will use the Cockcroft -Gault caculation. Measured creatinine clearance will be done locally only if needed.
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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] 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].
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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.8.5 | 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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |