E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glioblastoma Multiforme |
Glioblastoma Multiforme |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent Glioblastoma, a rare and aggressive type of brain tumor. |
Glioblastoma recurrente, un tipo de tumor cerebral agresivo y poco común. |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Overall Survival and Progression Free survival according to RANO criteria and assessed at interim analysis. |
Supervivencia global y supervivencia libre de progresión según criterios RANO y evaluados en análisis intermedio. |
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E.2.2 | Secondary objectives of the trial |
Progression Free Survival according to RANO criteria, Objective Response Rate, Overall Survival in the subgroup with EGFRvIII mutation. |
Supervivencia libre de progresión según criterios RANO, tasa de respuesta objetiva, supervivencia global en el subgrupo con la mutación EGFRvIII |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is a pharmacogenetic sub-study where the samples will be stored at AbbVie. There is also an optional translational and genetic sub-study where the samples will be biobanked with EORTC. |
Hay un subestudio farmacogenético en el cual las muestras serán almacenadas en AbbVie. También hay un subestudio translacional y genético opcional en el cual las muestras serán bioalmacenadas con la EORTC. |
|
E.3 | Principal inclusion criteria |
1. Histologically confirmed de novo (primary) GBM with unequivocal tumor progression or recurrence. 2. In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy 3. Age ? 18 years 4. Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial. 5. Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of EGFR amplification 6. Presence of EGFR amplification confirmed by central assessment; patients with undetermined EGFR status are excluded 7. WHO Performance status 0 - 2 8. No more than one line of chemotherapy (concurrent and adjuvant TMZ based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization. |
1. GMB de novo (primario) confirmado histológicamente con progresión tumoral o recurrencia inequívoca. 2. En caso de análisis en el momento de primera progresión: al menos 3 meses tras el fin de la radioterapia o progresión tumoral claramente fuera del campo de radiación o progresión tumoral inequívoca demostrada por cirugía/biopsia 3. Edad ? 18 años 4. Ausencia de cualquier factor psicológico, familiar, sociológico o geográfico que pudiera interferir en la adherencia con el protocolo del estudio y el calendario de seguimiento; tales condiciones deberán ser evaluadas con el paciente previo al registro en el ensayo 5. Disponibilidad de material biológico adecuado (tumor incluido en parafina fijado por formalina [FFPE]) para el análisis centralizado de amplificación de EGFR
6. Presencia de amplificación de EGFR confirmada por evaluación central; los pacientes con EGFR indeterminado están excluidos 7. Estado funcional de OMS entre 0 y 2 8. No más de una línea de tratamiento (la quimioterapia concurrente y adyuvante basada en TMZ incluyendo la combinación con otro producto en investigación es considerada una línea de tratamiento). La quimioterapia se debe haber completado al menos 4 semanas antes de la randomización |
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E.4 | Principal exclusion criteria |
1. Prior treatment with nitrosoureas 2. Prior treatment with bevacizumab 3. Previous exposure to EGFR targeted agents, including EGFRvIII targeting agents 4. Prior discontinuation of temozolomide chemotherapy for toxicity reasons 5. Prior RT with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven 6. Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix 7. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization. |
1. Tratamiento previo con nitrosureas 2. Tratamiento previo con bevacizumab 3. Exposición previa a agentes dirigidos a EGFR, incluyendo los dirigidos a EGFRvIII 4. Previa discontinuación de quimioterapia de temozolomida por motivos toxicológicos 5. RT previa con una dosis mayor de 65 Gy, cirugía esterotáctica o braquiterapia a no ser que la recurrencia esté comprobada histológicamente 6. Otras malignidades previas, excepto por cualquier otra malignidad previa que fuera tratada con intención curativa más de 5 años antes de la randomización, y excepto por carcinoma de células basales de la piel limitado y adecuadamente controlado, carcinoma escamoso de la piel o carcinoma in situ de cérvix. 7. Las mujeres con capacidad de procrear deben tener un resultado de embarazo en suero o en orina (sensibilidad mínima 25 IU/L o unidades de HCG equivalentes) negativo dentro de las 72 horas previas a la randomización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival and Progression Free survival according to RANO criteria and assessed at interim analysis. |
Supervivencia global y supervivencia libre de progresión según criterios RANO y evaluados en análisis intermedio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall Survival at final analysis and Progression Free Survival at interim futility analysis after observation of 45 PFS events. |
Supervivencia global en análisis final y supervivencia libre de progresión en análisis de futilidad intermedio tras la observación de 45 eventos de PFS |
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E.5.2 | Secondary end point(s) |
? Progression Free Survival ? Overall Response Rate (ORR) ? Overall Survival in the subgroup with Epithelial Growth Factor Receptor (EGFRvIII) mutation. |
? Supervivencia libre de progresión ? Tasa de respuesta global ? Supervivencia global en el subgrupo con mutación en el receptor del factor de crecimiento epidermoide (EGFRvIII) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? Progression Free Survival as assessed by RANO from date of randomization to date of first objective progression (or death). ? The overall response rate will be evaluated at each assessment of disease according to RANO criteria. ? Subgroup with EGFR vIII mutation will be measured up to 28 months (study length), until death, or lost to follow up. |
? Supervivencia libre de progresión evaluada por RANO desde fecha de randomización a fecha de primera progresión objetiva (o muerte) ? La tasa de respuesta global será analizada en cada evaluación de la enfermedad según criterios RANO ? El subgrupo con la mutación EGFRvIII será analizado hasta 28 meses (duración del estudio), hasta muerte o hasta pérdida de seguimiento. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Translational research |
Investigación translacional |
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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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Finland |
France |
Germany |
Hungary |
Ireland |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Puerto Rico |
Singapore |
Spain |
Switzerland |
Taiwan |
United Kingdom |
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
|
Subjects will be followed until death or lost to follow up. |
Los pacientes serán seguidos hasta muerte o hasta pérdida de seguimiento. |
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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 | 18 |
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 | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |