E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular carcinoma |
Carcinoma epatocellulare |
|
E.1.1.1 | Medical condition in easily understood language |
Liver cancer |
Tumore del fegato |
|
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 | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of cabozantinib in combination with atezolizumab versus sorafenib in subjects with advanced HCC who have not received previous systemic anticancer therapy. An exploratory objective is to evaluate the single-agent activity of cabozantinib in this patient population. |
L'obiettivo primario dello studio è valutare l'efficacia di cabozantinib in associazione con atezolizumab rispetto a sorafenib in soggetti con carcinoma epatocellulare avanzato che non sono stati sottoposti a precedente terapia antitumorale sistemica. Un obiettivo esplorativo è valutare l'attività come agente singolo di cabozantinib in questa popolazione di pazienti. |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
L'obiettivo secondario è valutare l'attività di cabozantinib come agente singolo rispetto a sorafenib in soggetti con carcinoma epatocellulare avanzato che non sono stati sottoposti a precedente terapia antitumorale sistemica. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histological or cytological diagnosis of HCC. - The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE). - Measurable disease per RECIST 1.1 as determined by the Investigator. - Barcelona Clinic Liver Cancer (BCLC) stage Category B or C. - Child-Pugh Score of A. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. |
- Diagnosi istologica o citologica di carcinoma epatocellulare. - La malattia del soggetto non risponde a un approccio di trattamento curativo (ad es. trapianto, intervento chirurgico, terapia ablativa) o a terapia locoregionale (ad es. chemioembolizzazione transarteriosa [TACE]). - Malattia misurabile, in conformità con RECIST 1.1, a giudizio dello sperimentatore. - Stadiazione BCLC (Barcelona Clinic Liver Cancer) di Categoria B o C. - Punteggio A secondo Child-Pugh. - Performance status secondo l'ECOG (Eastern Cooperative Oncology Group) 0-1. |
|
E.4 | Principal exclusion criteria |
- Fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma. - Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and ICIs. Subjects who have received local intratumoral or arterial chemotherapy are eligible. Subjects who have received any local anticancer therapy within 28 days prior to randomization are ineligible - Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization. - Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization. - Concomitant anticoagulation with oral anticoagulants. |
- Carcinoma fibrolamellare, carcinoma epatocellulare sarcomatoide o colangiocarcinoma epatocellulare misto. - Precedente terapia antitumorale sistemica per carcinoma epatocellulare avanzato, inclusi tra gli altri chemioterapia, inibitori delle chinasi a piccole molecole e inibitori del checkpoint immunitario (ICI). I soggetti che sono stati sottoposti a chemioterapia locale intratumorale o arteriosa sono idonei. I soggetti che sono stati sottoposti a qualsiasi terapia antitumorale locale nei 28 giorni precedenti alla randomizzazione non sono idonei. - Radioterapia per metastasi ossee nelle 2 settimane precedenti alla randomizzazione o qualsiasi altra radioterapia nelle 8 settimane precedenti alla randomizzazione. - Metastasi cerebrali note o malattia epidurale cranica, a meno che non sia adeguatamente trattata con radioterapia e/o intervento chirurgico (radiochirurgia inclusa) e stabile per almeno 8 settimane precedenti alla randomizzazione. - Terapia concomitante con anticoagulanti orali. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Duration of Progression Free Survival (PFS) per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)
• Duration of Overall Survival (OS) |
• Durata della sopravvivenza libera da progressione (PFS) secondo criteri di risposta valutabili in tumori solidi, versione 1.1 (RECIST 1.1), valutata da un Comitato di radiologia indipendente in cieco (BIRC) • Durata della sopravvivenza complessiva (OS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Duration of PFS: The primary analysis of PFS is event-driven and will be conducted after at least 241 events have been observed in the first 342 subjects that are randomized (based upon Greenwich Mean Time randomization date/time values) to the experimental (cabozantinib and atezolizumab) arm and control (sorafenib) arm.
• Duration of OS: The primary analysis of OS is event-driven and will be conducted after at least 346 deaths have been observed in all subjects who are randomized to the experimental (cabozantinib plus atezolizumab) arm and control (sorafenib) arm, regardless of whether any study treatment or the correct study treatment is received. |
• Durata di PFS: L’analisi primaria di PFS è guidata dagli eventi e sarà condotta dopo che sono stati osservati almeno 241 eventi nei primi 342 soggetti randomizzati (valori di data/tempo di randomizzazione basati sull’ora di Greenwich) nel braccio sperimentale (cabozantinib e atezolizumab) e nel braccio di controllo (sorafenib). • Durata di OS: L’analisi primaria di OS è guidata dagli eventi e sarà condotta dopo che sono stati osservati almeno 346 decessi tra tutti i soggetti randomizzati nel braccio sperimentale (cabozantinib più atezolizumab) e nel braccio di controllo (sorafenib), indipendentemente dal fatto che sia stato ricevuto qualsiasi trattamento di studio o il trattamento di studio corretto. |
|
E.5.2 | Secondary end point(s) |
PFS per RECIST 1.1 by BIRC for the single-agent cabozantinib arm vs the control arm (sorafenib) |
PFS in base ai criteri RECIST 1.1 da parte del BIRC per il braccio con cabozantinib come agente singolo rispetto al braccio di controllo (sorafenib) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The analysis of PFS as a secondary endpoint is event-driven and will be conducted after at least 282 events have been observed in all subjects who are randomized to the single-agent cabozantinib and control arms, regardless of whether any study treatment or the correct study treatment is received |
L’analisi di PFS come endpoint secondario è guidata dagli eventi e sarà condotta dopo che sono stati osservati almeno 282 eventi in tutti i soggetti randomizzati nel braccio con cabozantinib come agente singolo e nel braccio di controllo, indipendentemente dal fatto che sia stato ricevuto qualsiasi trattamento di studio o il trattamento di studio corretto. |
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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 | No |
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) | 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 | Yes |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 91 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
Colombia |
Georgia |
Hong Kong |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Philippines |
Russian Federation |
Singapore |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Hungary |
Ireland |
Italy |
Netherlands |
Poland |
Romania |
Spain |
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
|
Study Completion by Country or by Site: At the time the Maintenance Phase is initiated, the study will be considered complete at sites and in countries where all subjects have completed post-treatment safety follow-up. |
Completamento dello studio per Paese o Centro: nel momento in cui avrà inizio la Fase di mantenimento, lo studio sarà considerato completato nei centri e nei paesi in cui tutti i soggetti abbiano completato il follow-up di sicurezza post-trattamento. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |