E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Renal Cell Carcinoma |
Carcinoma a cellule renali in stadio avanzato |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced kidney cancer |
Cancro al rene in stadio avanzato |
|
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 compare the progression-free survival (PFS) of subjects with refractory advanced renal cell carcinoma (RCC) randomized to treatment with tivozanib hydrochloride (tivozanib) or sorafenib as assessed by blinded independent radiological review (IRR) of computerized tomography (CT) or magnetic resonance imaging
(MRI). |
Valutare la sopravvivenza libera da progressione (PFS) in soggetti con carcinoma a cellule renali (RCC) in stadio avanzato refrattario randomizzati al trattamento con tivozanib cloridrato (tivozanib) o sorafenib, come determinata da una valutazione radiologica indipendente (IRR) in cieco della tomografia computerizzata (TC) o della risonanza magneticha (RM) |
|
E.2.2 | Secondary objectives of the trial |
- To compare the overall survival (OS) of subjects randomized to treatment with tivozanib or sorafenib. - To compare objective response rate (ORR) and duration of response (DoR) of subjects randomized to treatment with tivozanib or sorafenib. - To compare the safety and tolerability of tivozanib and sorafenib. |
- Valutare la sopravvivenza generale (OS) dei soggetti randomizzati al trattamento con tivozanib vs. sorafenib - Valutare il tasso di risposta obiettiva (ORR) e la durata della risposta (DoR) nei soggetti randomizzati al trattamento con tivozanib o sorafenib - Valutare la sicurezza e la tollerabilit¿ di tivozanib e sorafenib
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. = 18-years of age. 2. Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib. 3. Subjects must have recovered from the AEs of prior therapy or returned to baseline. Controlled AEs such as hypothyrodism or hypertension are permitted. 4. Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, and unclassified RCC are excluded). 5. Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy = 3 months. 8. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment. 9. Ability to give written informed consent and comply with protocol. |
1. Età =18 anni 2. Soggetti con RCC metastatico che hanno fallito 2 o 3 precedenti regimi terapeutici sistemici, uno dei quali a base di un TKI VEGFR diverso da sorafenib o tivozanib. 3. Risoluzione degli eventi avversi della terapia precedente o ritorno allo stato basale.Sono consentiti AE controllati come ipotiroidismo o ipertensione. 4. Conferma istologica o citologica di RCC con componente a cellule chiare (con l’esclusione dei soggetti con carcinoma papillare puro o altre istologie non a cellule chiare, compresi il carcinoma del dotto collettore, midollare, cromofobo, e gli RCC non classificabili) 5. Malattia misurabile in base ai criteri RECIST (Response Evaluation Criteria in Solid Tumors) versione 1.1 6. Indice di performance ECOG (Eastern Cooperative Oncology Group) pari a 0 o 1 7. Aspettativa di vita =3 mesi 8. Per le donne in età fertile, esito negativo al test di gravidanza prima dell’arruolamento 9. Soggetti in grado di fornire il consenso informato scritto e di rispettare i requisiti del protocollo |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with sorafenib or tivozanib. 2. More than 3 prior regimens for metastatic RCC. 3. Known central nervous system (CNS) metastases other than stable, treated brain metastases. Subjects with previously treated brain metastasis will be allowed if the brain metastasis has been stable by neuroimaging without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery). 4. Significant cardiovascular disease 5. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug 6. Significant bleeding disorders 7. Currently active second primary malignancy 8. Pregnant or lactating females. 9. Participation in another interventional protocol. |
1. Precedente trattamento con sorafenib o tivozanib 2. Più di 3 precedenti regimi terapeutici per il RCC metastatico 3. Metastasi note a carico del sistema nervoso centrale (SNC), diverse da metastasi cerebrali stabili trattate. I soggetti con precedenti metastasi cerebrali trattate potranno essere inclusi nello studio qualora un esame di immagine confermi che la metastasi è rimasta stabile per almeno 3 mesi dopo una precedente terapia (radioterapia o intervento chirurgico) senza essere stata trattata con steroidi 4. Patologie cardiovascolari significative 5. Disturbo tromboembolico o vascolare significativo nei 6 mesi precedenti la somministrazione della prima dose di farmaco in studio 6. Disturbi emorragici significativi 7. Seconda neoplasia maligna primitiva correntemente in fase attiva 8. Donne in gravidanza o allattamento 9. Partecipazione a un altro protocollo interventistico
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the PFS of subjects dosed with tivozanib with those subjects dosed with sorafenib |
Paragonare la PFS dei soggetti trattati con tivozanib con quella dei soggetti trattati con sorafenib. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis will be done at the time of the final PFS analysis |
L’analisi verrà effettuata al momento della valutazione della PFS finale |
|
E.5.2 | Secondary end point(s) |
¿ To compare the OS between the 2 treatment arms by using stratified Log-rank test and the stratification factors included in the primary analysis. ¿ To analyze OS, ORR, and DoR using the investigator and independent radiological review assessments.
|
¿ Confrontare la OS tra i 2 bracci di trattamento mediante test dei ranghi logaritmici stratificato e i fattori di stratificazione inclusi nell¿analisi primaria ¿ Valutare OS, ORR e DoR utilizzando le valutazioni degli sperimentatori e dell¿IRR
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The interim OS analysis will be done at the time of the final PFS analysis. The final OS analysis will be performed when all subjects have been lost to follow-up, have withdrawn consent, or have died, or when all subjects in follow-up have been on-study for at least 2 years, whichever occurs first. |
L'analisi di OS ad interim sar¿ effettuata al momento della valutazione della PFS finale. L'analisi di OS finale sar¿ effettuata quando tutti i soggetti saranno stati persi al follow-up, avranno ritirato il consenso, o saranno deceduti, oppure quando tutti i soggetti in follow-up saranno stati in studio per almeno 2 anni, qualunque delle due avvenga prima. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tollerabilit¿ |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 | Information not present in EudraCT |
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 |
Canada |
Israel |
New Zealand |
United States |
Belgium |
Denmark |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
Sweden |
United Kingdom |
Czechia |
|
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
|
End of the trial - when all subjects have been lost to follow-up, have withdrawn consent, or have died, or when all subjects in follow-up have been on-study for at least 2 years, whichever occurs first. |
Conclusione della sperimentazione - quando tutti i soggetti sono stati persi al follow-up, hanno ritirato il consenso, o sono deceduti, oppure quando tutti i soggetti in follow-up sono stati in studio per almeno 2 anni, qualunque delle due avvenga prima. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |