E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non Small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
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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 primary efficacy objective is to compare overall survival (OS) in patients treated with carboplatin, paclitaxel and sorafenib to OS in patients treated with carboplatin, paclitaxel and placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include tumor response, duration of response, progression free survival and patient reported outcomes.
A tertiary objective of this study is to evaluate biomarkers that may relate the pharmacological mechanism of action of sorafenib to its antitumor activity. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
•Stage IIIB (with pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC •No prior chemotherapy •Prior local radiotherapy is allowed if it is completed at least 3 weeks prior to the first dose of study drug. •Prior surgery is allowed if it is performed at least 4 weeks prior to the first dose of study drug. •Age greater than or equal to 18 years old. •ECOG Performance Status of 0 or 1 •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 greater than or equal to 9.0 g/dl •Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 •Platelet count greater than or equal to 100,000/mm3 •Total bilirubin less than or equal to 1.5 times the upper limit of normal •ALT and AST less than or equal to 2.5 x upper limit of normal (less than or equal to 5 x upper limit of normal for patients with liver involvement) •INR less than or equal to 1.5 and aPTT within normal limits •Creatinine less than or equal to 1.5 times the upper limit of normal •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment •Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib. •Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
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E.4 | Principal exclusion criteria |
•Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for NSCLC •Cardiac disease: Congestive heart failure greater than class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months •Known brain metastasis. Patients with neurological symptoms should undergo at CT scan/MRI of the brain to exclude brain metastasis. •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy •Uncontrolled hypertension defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg, despite optimal medical management. •Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C •Active clinically serious infections greater than CTCAE Grade 2 •Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months •Pulmonary hemorrhage/bleeding event greater than or equal to CTCAE Grade 2 within 4 weeks of first dose of study drug •Any other hemorrhage/bleeding event greater than or equal to CTCAE Grade 3 within 4 weeks of first dose of study drug •Serious, non-healing wound, ulcer, or bone fracture •Evidence or history of bleeding diathesis or coagulopathy •Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug •Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin (1 mg po qd) is permitted if the INR is less than or equal to 1.5. Low-dose aspirin is permitted •Use of St John’s Wort or rifampin (rifampicin) •Known or suspected allergy to sorafenib or any agent given in the course of this trial •Previous cancer that is distinct in primary site or histology from NSCLC EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis] or any cancer curatively treated greater than 3 years prior to study entry. •Concurrent cancer that is distinct in primary site or histology from NSCLC •Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results •Any condition that impairs patient’s ability to swallow whole pills •Any malabsorption condition
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival (OS) of the sorafenib in combination with paclitaxel and carboplatin group versus placebo in combination with carboplatin and paclitaxel group. All randomized patients (ITT Population) will be included in the primary analyses. One-sided alpha of 0.025 will be used for the OS analysis. Overall survival is defined as the time from randomization to death due to any cause. Patients alive at the time of analysis will be censored at their last date of follow-up. In the analysis of OS, the two treatment groups (sorafenib and placebo) will be compared using a one-sided log-rank test with an overall alpha of 0.025 stratified by the same stratification factors as randomization: ECOG PS (0 vs. 1), histology (squamous vs. non-squamous), Stage ( IIIB with pleural or pericardial effusion vs. Stage IV), and region (North America, South America, Eastern Europe, and Northern/Western Europe). Kaplan-Meier estimates and survival curves will also be presented for each treatment group.
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Health Economics/Patient Reported Outcomes |
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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) | Yes |
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.8.6 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 | Information not present in EudraCT |
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 trial is defined as the close of the database (clean database). The last visit of the last subject will occur approximately 7 days after the stop of study drug therapy. All subjects will enter a follow-up period and be followed until death. The close of the database is planned for approximately 6 weeks after the last patient's death or removal from the trial. |
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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 |