E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patient in advanced pancreatic neuroendocrine tumors |
Pacientes adultos con tumores neuroendocrinos pancreáticos avanzados. |
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E.1.1.1 | Medical condition in easily understood language |
Adult patient with pancreatic neuroendocrine tumors pNET |
Pacientes adultos con tumores neuroendocrinos pancreaticos pNET |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068916 |
E.1.2 | Term | Pancreatic neuroendocrine tumor metastatic |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To estimate the efficacy of BEZ235 in adult patients with advanced (unresectable or metastatic) pNET (PFS) |
Estimar la eficacia de BEZ235 en pacientes adultos con pNET (irresecable o metastásico) |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of BEZ235 therapy To evaluate the efficacy of BEZ235 per modified RECIST v1.1 (Overall Response Rate, Disease Control Rate, Duration of Response ) |
Evaluar la seguridad y tolerabilidad de la terapia con BEZ235 Evaluar la eficacia de BEZ235 según los criterios RECIST v1.1 (Tasa de respuesta global, tasa de control de la enfermedad, duración de la respuesta) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: Unresectable or metastatic, histologically confirmed low or intermediate grade pancreatic neuroendocrine tumor with radiological evidence of disease progression since last treatment. Refractory disease to treatment with mTOR inhibitor, Measurable disease per RECIST Version 1.1 using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), Prior or concurrent therapy with SSA is permitted;a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment; Other protocol defined inclusion/exclusion criteria may apply. |
Pacientes con TNEP (irresecable o metastásico) avanzado confirmado mediante histología de grado bajo o intermedio y que muestren signos radiológicos de progresión de la enfermedad desde el último tratamiento. Pacientes cuya enfermedad sea refractaria al tratamiento con el inhibidor mTOR. Enfermedad medible según RECIST Versión 1.1 utilizando una tomografía computarizada (TC) o una resonancia magnética (RM). Se permite seguir un tratamiento previo o concurrente con AS a una dosis estable al menos 2 meses antes del inicio del estudio y debe mantenerse dicha dosis mientras reciben el tratamiento del estudio. Pueden aplicar otros criterios de inclusión/exclusión definidos en el protocolo. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: Previous treatment with any PI3K or AKT inhibitor, Discontinuation prior mTOR inhibitor therapy due to toxicity, Poorly differentiated neuroendocrine carcinoma, highgrade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma, Cytotoxic chemotherapy, targeted therapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to enrolment in the study, Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment More than 3 prior systemic treatment regimens, Other protocol defined inclusion/exclusion criteria may apply |
Pacientes que hayan recibido un tratamiento anterior con cualquier inhibidor PI3K y/o inhibidor AKT para el tratamiento del TNEP. Pacientes que hayan suspendido el tratamiento anterior con inhibidores mTOR debido a una toxicidad. Pacientes con un carcinoma neuroendocrino poco diferenciado, un carcinoma neuroendocrino de grado alto, adenocarcinoide, carcinoide de células globoides y carcinoma de células pequeñas. 4. Pacientes que se hayan sometido a quimioterapia citotóxica, terapia selectiva, inmunoterapia, radioterapia o una intervención quirúrgica importante en un plazo de 4 semanas antes de su inclusión en el estudio. Pacientes que se hayan sometido a un tratamiento con embolización arterial hepática en los últimos 6 meses (1 mes si existen otros puntos de enfermedad medible) o crioablación/ablación por radiofrecuencia de metástasis hepático 2 meses después de la inclusión. Pacientes con más de 3 tratamientos sistémicos anteriores. Pueden aplicar otros criterios de inclusión/exclusión definidos en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS rate at 16 weeks according to local radiological assessment per modified RECIST v1.1 |
El objetivo principal es determinar la eficacia de BEZ235 en pacientes adultos con TNEP (irresecable o metastásico) avanzado basándose en la tasa de SLP a las 16 semanas conforme a la evaluación radiológica local. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to approx 18 months |
hasta alcanzar 18 meses aproximadamente |
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E.5.2 | Secondary end point(s) |
Frequency and severity of adverse events;other safety data as considered appropriate Overall Response Rate, Disease Control Rate, Duration of Response ) |
Frecuencia y severidad de los acontecimientos adversos, otros datos de seguridad que se consideren apropiados. Tasa de respuesta global, tasa de control de la enfermedad, duración de la respuesta. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to approx. 18 months for all secondary endpoint |
hasta alcanzar 18 meses aproximadamente para todos los objetivos secundarios |
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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 | 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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Korea, Republic of |
United States |
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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 study (last patient last visit) will occur after all patients have completed their last assessment as per protocol. The final analysis will be conducted after all enrolled patients have completed the study |
Si se suspende en la etapa 1, se declarará fin de estudio cuando todos los pacientes hayan completado el periodo de seguimiento de seguridad (al menos 30 días). Si el estudio prosigue con la etapa 2, el análisis principal de eficacia se realizará tras observarse 50 acontecimientos. El estudio finalizará cuando el periodo de tratamiento y el seguimiento de la seguridad, la eficacia y la supervivencia hayan finalizado o cuando el estudio haya finalizado de forma prematura. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 32 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 32 |
E.8.9.2 | In all countries concerned by the trial days | 0 |