E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glioblastoma in recurrence/progression after surgery (or biopsy), radiotherapy and chemotherapy with temozolomide |
Glioblastoma in recidiva o progressione dopo chirurgia (o biopsia), radioterapia e chemioterapia con Temozolomide |
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E.1.1.1 | Medical condition in easily understood language |
Glioblastoma in recurrence/progression |
Glioblastoma in recidiva o progressione |
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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 |
To evaluate the efficacy of Ortataxel in terms of PFS-6, defined as the percentage of patients who are alive and progression free at 6 months after the randomization. Fotemustine will act as a calibration arm |
Valutare l’efficacia di Ortataxel in termini di PFS-6, definita come la percentuale di pazienti che sono vivi e liberi da progressione dopo 6 mesi dalla data di randomizzazione. Il braccio con Fotemustina servirà da braccio di “calibrazione”. |
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E.2.2 | Secondary objectives of the trial |
To evaluate:
- percentage of survival patients after 9 months from the randomization.
- percentage of patients who are judged by the Investigators to have an objective response as determined by the RANO criteria.
- the treatment compliance.
- the safety profile. |
- percentuale di pazienti che sono vivi a 9 mesi dalla data di randomizzazione.
- percentuale di pazienti che hanno risposta oggettiva secondo quanto determinato dai criteri RANO.
- La compliance al trattamento in studio
- Il profilo di sicurezza.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed GBM.
- GBM in recurrence/progression after surgery, standard radiotherapy and chemotherapy with Temozolomide.
- Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria.
- No more than one prior line of chemotherapy (Temozolomide).
- Recovery from the toxic effects of prior therapy.
- Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:
a) Surgery must have confirmed the recurrence.
b) A minimum of 14 days must have elapsed from the day of surgery to randomization. For core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization.
c) Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization.
- Age ≥ 18 years.
- Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator.
- Karnofsky-PS ≥ 60%.
- Stable or decreasing dose of corticosteroids within 5 days prior to randomization.
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- Pazienti con glioblastoma
- Glioblastoma in recidiva o progressione confermato istologicamente alla prima recidiva dopo chirurgia, trattamento standard con radioterapia e Temozolamide.
- Conferma radiologica di progressione o recidiva in accordo ai criteri RANO.
- Non più di una precedente linea di chemioterapia (Temozolamide).
- Completa risoluzione di tutti gli effetti tossici delle terapie precedenti.
- Pazienti che hanno subito recentemente una chirurgia per recidiva o progressione del tumore sono eligibili se la chirurgia ha confermato la recidiva e sono trascorsi almeno 14 giorni dalla data di chirurgia alla data di randomizzazione. In seguito ad agobiopsia o agoaspirato sono sufficienti 7 giorni.
- Capacità di comprendere e rilasciare il consenso informato scritto per la partecipazione allo studio.
- Età ≥ 18 anni.
- Karnofsky-PS ≥ 60%.
- Dose di corticosteroidi stabile o in diminuzione nei 5 giorni precedenti la randomizzazione |
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E.4 | Principal exclusion criteria |
- Patients unable to undergo brain MRI scans with gadolinium (iv).
- Pre-existing peripheral neuropathy, grade ≥ 2.
- History of intracranial abscess within 6 months prior to randomization.
- Anticipation of need for major surgical procedure during the course of the trial.
- Treatment with enzyme inducing antiepileptic agents was not allowed. However, patients whose anticonvulsant was changed to a non-enzymeinducing antiepileptic drug were eligible for entry after a 1-week ‘‘washout’’ period.
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- Pazienti che non possono essere sottoposti a risonanza magnetica (MRI) con gadolinio (via endovenosa) come mezzo di contrasto.
- Pre-esistente neuoropatia periferica di grado ≥ 2.
- Ascesso intracranico nei 6 mesi precedenti la randomizzazione. Procedura chirurgica maggiore programmata.
- Trattamento con agenti antiepilettici induttori enzimatici. Tuttavia, pazienti passati ad una terapia anticonvulsivante con un agente antiepilettico non induttore enzimatico sono eligibili dopo una settimana di “washout”
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E.5 End points |
E.5.1 | Primary end point(s) |
6-months progression-free survival (PFS-6), defined as the percentage of patients who are alive and progression free at 6 months after the randomization
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PFS-6, definita come la percentuale di pazienti che sono vivi e liberi da progressione dopo 6 mesi dalla data di randomizzazione |
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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) |
PFS
OS-9
ORR
Dose-intensity
Percentage of patients with dose and/or time modifications
Percentage of premature withdrawals
Incidence, nature, severity and seriousness of AEs
Maximum toxicity grade experienced by each patient for each specific toxicity
Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
Patients with at least a SAE
Patients with at least a serious adverse drug reaction (SADR)
Patients with at least a suspect unexpected serious adverse reaction (SUSAR).
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PFS
OS-9
ORR
Dose di farmaco effettivamente somministrato per unità di tempo
Percentuale di pazienti che hanno avuto una modifica di dose e/o tempi
Percentuale di pazienti che si sono ritirati dallo studio
Incidenza, natura, severità e serietà di un AE
Massimo grado di tossicità avuta da ciascun paziente per ciascuna tossicità
Percentuale di pazienti con tossicità di grado 3-4
Pazienti con almeno un SAE
Pazienti con almeno un SADR
Pazienti con almeno un SUSAR |
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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 | 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 | 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 | 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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LVLS, at least 9 months after randomization |
Ultima visita dell'ultimo paziente, almeno 9 mesi dopo la randomizzazione |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |