E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
NSCLC with EGFR mutation |
NSCLC met EGFR mutatie |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
To assess partial response rate according to RECIST 1.1 |
het bepalen van de objectieve response rate volgens RECIST 1.1 |
|
E.2.2 | Secondary objectives of the trial |
Progression-free survival, disease controle rate and toxicity |
Progressie-vrije overleving, disease cotrol rate en toxiciteit |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed stage IV non-squamous NSCLC patients.
• Patients must have been detected with an activating EGFR mutation at baseline and must have yet progressed on erlotinib, gefitinib or afatinib monotherapy in daily dose of 150 mg, 250 mg or 40 mg respectively. (Patients with unknown mutation status that have exhibited a response to these agents or stable disease for at least 6 months while on treatment with gefitinib or erlotinib are also eligible).
• Rebiopsy after having acquired resistance to TKI-treatment must have been performed and HER2-overexpression (positive immunohistochemistry staining) must have been detected.
• There must be at least one measurable disease site, according to RECIST 1.1 criteria.
• WHO performance status 0-2.
• Willing and able to comply with the study prescriptions.
• 18 years or older.
• Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study.
• Ability to give written informed consent before patient registration. |
• Histologisch bevestigd stadium IV NSCLC (geen plaveisel).
• Er moet een activerende EGFR-mutatie aangetoond zijn. De patient moet reeds progressie hebben op een TKI (erlotinib, gefitinib, afatinib in standaarddosering). Patiënten met onbekende mutatie status die een reactie op deze agentia of stabiele ziekte vertoonden ten minste 6 maanden op de behandeling met gefitinib of erlotinib komen ook in aanmerking ) .
• Er moet een herbiopt hebben plaatsgevonden na progressie op standaarddosering TKI en HER2 overexpressie moet zijn aangetoond met immunohistochemie (IHC).
• Er moet ten minste een meetbare lesie zijn, volgens RECIST 1.1 criteria .
• WHO performance status 0-2 .
• Bereid en in staat om te voldoen aan de studie voorschriften .
• 18 jaar of ouder .
• Niet zwanger bent of borstvoeding gevend en bereid om adequate contraceptieve maatregelen te nemen tijdens de studie.
• Mogelijkheid om schriftelijk toestemming te geven voorafgaand aan inclusie. |
|
E.4 | Principal exclusion criteria |
• No uncontrolled infectious disease.
• No other active malignancy.
• No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy or VATS biopsy) in the previous 4 weeks.
• No treatment with investigational drugs.
• No known hypersensitivity to trastuzumab-paclitaxel
• No symptomatic brain metastases.
• History of coronary artery disease, NYHA class III or IV and Left Ventricular Ejection Fraction (LVEF) of <45%. |
• Geen ongecontroleerde infectieuze ziekte.
• Geen andere actieve maligniteit.
• Geen grote operatie (met uitzondering van diagnostische procedures, zoals bijvoorbeeld mediastinoscopie of VATS biopsie) in de voorgaande 4 weken.
• Geen behandeling met experimentele geneesmiddelen.
• Geen bekende overgevoeligheid voor trastuzumab-paclitaxel
• Geen symptomatische hersenmetastasen.
• Geschiedenis van coronaire hartziekte, NYHA klasse III of IV en linker ventrikel ejectiefractie (LVEF) van <45%. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate |
Objectieve response rate volgens RECIST criteria |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 weeks of treatment |
na 6 weken behandeling |
|
E.5.2 | Secondary end point(s) |
disease controle rate, progression-free survival, toxicity |
Disease controle rate, progressie-vrije overleving, toxiciteit |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Einde van de studie |
|
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |