E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced non small cell lung cancer that harbours a K-Ras mutation |
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E.1.1.1 | Medical condition in easily understood language |
patients with advanced lung cancer with a K-Ras mutation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Efficacy of sorafenib and metformin in NSCLC with a K-RAS mutation as determined by the Rate of No Progression |
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E.2.2 | Secondary objectives of the trial |
duration of response • time to disease progression or death • survival |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically advanced NSCLC stage IIIB or IV harbouring a K-RAS mutation 2. Disease progression after at least 1 prior chemotherapy regimen that should include a platinum doublet 3. Prior surgery and/or localized irradiation is permitted provided that the irradiated lesion is not the only measurable lesion. 4. Age > 18 years. 5. ECOG Performance Status of 0-2 6. Life expectancy of at least 12 weeks 7. written informed consent |
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E.4 | Principal exclusion criteria |
1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arythmias requiring anti-arythmic therapy( beta blockers or digoxin are permitted) or uncontrolled hypertension. 2. History of HIV infection or chronic hepatitis B or C. 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 1 months from definitive radiotherapy and off steroids): 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main endpoint of the study is the rate of no progression at 6 weeks (NPR). This NPR is defined as the rate of subjects without progression (based on RECIST criteria) at 6 weeks after start of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks after start treatment |
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E.5.2 | Secondary end point(s) |
6.2.1 Response rate, Disease Control Rate and Response Duration
Each subject will be assigned a best objective response. This is defined as the best response recorded from the start of treatment until disease progression/recurrence (according to RECIST criteria). To be assigned the status of PR or CR, changes in tumour measurements must be confirmed by repeated assessments that should be performed no less than 4 weeks after the criteria for response are first met. The Disease Control Rate is defined as the number of CR+PR+SD patients. Objective response will be summarized in a descriptive manner. The analysis of duration of tumour response will be based on responding patients. Duration of response is defined as the time from first response to the time of documented disease progression or death (assuming confirmation of response at least 4 weeks after initial documentation). Subjects still responding to treatment at the time of analysis will be treated as censored observations for duration of response on the date of the last tumour assessment.
6.2.2 Progression Free survival
Progression free survival is defined as the time from date of informed consent to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. The actual date of tumour assessments will be used for this calculation. PFS for patients without disease progression or death at the time of analysis will be censored at the last date of tumour evaluation. PFS for patients who have no tumour assessments after baseline will be censored at day 1.
6.2.3 Overall Survival
Overall survival will be determined from the date of start of treatment to the date of death irrespective of the cause of death. Patients who have not died at the time of the final analysis will be censored at the date of last contact.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 study will be terminated after every patient had a follow up of at least 6 months. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |