E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuroendocrine carcinoma of the lung and thymus |
Neuro-endocrien carcinoom van de long en thymus |
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E.1.1.1 | Medical condition in easily understood language |
Neuroendocrine cancer of the lung and thymus |
Neuro-endocriene kanker van de long en zwezerik |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025064 |
E.1.2 | Term | Lung carcinoma |
E.1.2 | System Organ Class | 100000015855 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062476 |
E.1.2 | Term | Neuroendocrine tumor |
E.1.2 | System Organ Class | 100000019354 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of pasireotide LAR and everolimus alone or in combination in progressive patients with a well differentiated neuroendocrine tumor of the lung or thymus.
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Bestuderen van de werkzaamheid van pasireotide LAR en everolimus, alleen of in combinatie, bij progressieve patiënten met een goed gedifferentieerd neuro-endocrien carcinoom van de long of thymus |
|
E.2.2 | Secondary objectives of the trial |
Progression-free survival
Disease control rate
Time to Response
Duration of Response
Time from onset of the first objective tumor response
Time to progression
Biochemical response rate
Rate and severity of AEs |
Progressievrije overleving
Ziektebeheersing ratio
Tijd tot respons
Responsduur
Tijd start van de eerste objectieve tumorrespons
Tijd tot progressie
Biochemische respons ratio
Aantal en ernst van bijwerkingen
|
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histological confirmed advanced well differentiated carcinoma of the lung and thymus
• Patients of all treatment lines can be included
• At least one measurable lesion of disease on CT scan or MRI
• Radiological documentation of disease progression within 12 months prior to randomization
• Adequate liver, renal and bone marrow function
• WHO performancestatus 0-2
Other protocol-defined inclusion criteria may apply |
• Histologisch bevestigde gevorderde goed gedifferentieerd carcinoom van de long en thymus
• Patiënten afkomstig vanuit alle behandellijnen kunnen worden geincludeerd
• Minstens één meetbare laesie op CT scan of MRI
• Radiologisch rapport van ziekteprogressie van maximaal 12 maanden oud
• Adequate lever-, nier-, en beenmergfunctie
• WHO performance status 0-2
Andere inclusiecriteria welke in het protocol gedefineerd zijn, kunnen van toepassing zijn |
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E.4 | Principal exclusion criteria |
• Poorly differentiated neuroendocrine carcinoma
• Non-neuroendocrine thymoma
• Patients with severe functional disease requiring symptomatic treatment with somatostatin analogs
• Prior therapy with mTOR inhibitors
• History of liver disease
• Baseline QTcF> 470 msec
• Uncontrolled diabetes mellitus despite adequate therapy
Other protocol-defined exclusion criteria may apply
|
• Slecht gedifferentieerd neuro-endocrien carcinoom
• Niet neuro-endocrien thymoma
• Patiënten met ernstige functionele ziekten welke symptomatische behandeling met somatostatine analogen behoeven
• Voorgaande behandeling met mTOR remmers
• Leverziekte in het verleden
• Baseline QTcF> 470 msec
• Ongecontrolleerde diabetes mellitus ondanks adequate behandeling
Andere exclusiecriteria welke in het protocol gedefineerd zijn, kunnen van toepassing zijn |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients progression-free at 9 months |
Aandeel van progressievrije patiënten na 9 maanden |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Time from first study drug administration to objective tumor progression or death from any cause
2. Proportion of patients showing a best overall response of complete response, partial response or stable disease during 12 months of treatment
3. Time from start of treatment to the first observed objective tumor response
4. Time from onset of the first objective tumor response to objective tumor progression or death from any cause
5. Time from date of start of treatment to date of event defined as the first documented progression or deadth due to underling disease
6. Percentage of patients showing normalization or a decrease > or equal 30% of serum CgA compared to baseline
7. Rate and severity of AEs |
1. Tijd van eerste studiemedicatie-inname tot objectieve tumorprogressie of overlijden om willekeurig welke reden
2. Aandeel van patiënten met een beste overall respons uit volledige respons, gedeeltelijke respons of stabiele ziekte gedurende 12 maanden van behandeling
3. Tijd van start behandeling tot eerste geobserveerde objectieve tumorrespons
4. Tijd van start eerste objectieve tumorrespons tot objectieve tumorprogressie of overlijden om willekeurig welke reden
5. Tijd van start van behandeling tot datum van eerst gedocumenteerde progressie of overlijden door ten grondslag liggende ziekte
6. Percentage van patiënten met normalisatie of een afname van 30% of meer van serum CgA ten opzichte van baseline
7. Ratio en ernst van AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Every 3 months up to 1 year
2. Every 3 months up to 1 year
3. Every 3 months up to 1 year
4. Every 3 months up to 1 year
5. Every 3 months up to 1 year
6. Every 3 months up to 1 year
7. Week 2, 3, 4 and 7; every month up to 56 days after end of study treatment |
1. Iedere 3 maanden gedurende 1 jaar
2. Iedere 3 maanden gedurende 1 jaar
3. Iedere 3 maanden gedurende 1 jaar
4. Iedere 3 maanden gedurende 1 jaar
5. Iedere 3 maanden gedurende 1 jaar
6. Iedere 3 maanden gedurende 1 jaar
7. Week 2, 3, 4 en 7, en daarna iedere maand tot 56 dagen na de laatste studiebehandeling. |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 | No |
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 |
Denmark |
France |
Germany |
Greece |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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
|
The end of the study is defined as the last visit two years after treatment start of the last evaluable patient for the primary endpoint or when all patients have progressed whichever comes first |
Het einde van de studie is gedefinieerd als het laatste studiebezoek 2 jaar na start van de behandeling van de laatste evalueerbare patient voor het primaire eindpunt of wanneer alle patienten progressief zijn geworden, welke van de twee scenarios zich het eerst voordoet. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |