E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intermediate-stage Hepatocellular Carcinoma (HCC) |
Carcinoma epatocellulare (HCC) in stadio intermedio |
|
E.1.1.1 | Medical condition in easily understood language |
Intermediate-stage Liver Cancer |
Carcinoma al fegato in stadio intermedio |
|
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 | LLT |
E.1.2 | Classification code | 10049010 |
E.1.2 | Term | Carcinoma hepatocellular |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
1) To compare TTTP of nivolumab and ipilimumab plus TACE (Arm A) to nivolumab placebo and ipilimumab placebo plus TACE (Arm C) in all randomized participants.
2) To compare the OS of Arm A to Arm C in all randomized participants. |
1) Confrontare il tempo alla progressione della TACE (TTTP) di nivolumab e ipilimumab più TACE (Braccio A) rispetto a placebo di nivolumab e placebo di ipilimumab più TACE (Braccio C) in tutti i partecipanti randomizzati. 2) Confrontare la sopravvivenza complessiva (OS) del Braccio A rispetto al Braccio C in tutti i partecipanti randomizzati. |
|
E.2.2 | Secondary objectives of the trial |
1) To compare TTTP of nivolumab and ipilimumab placebo plus TACE (Arm B) to Arm C in all randomized participants.
2) To compare the OS of Arm B to Arm C in all randomized participants.
3) To compare EFS of Arm A vs Arm C and Arm B vs Arm C in all randomized participants.
4) To compare PFS of Arm A vs Arm C and Arm B vs Arm C in all randomized participants. |
1) Confrontare il TTTP di nivolumab e placebo di ipilimumab più TACE (Braccio B) rispetto al Braccio C in tutti i partecipanti randomizzati. 2) Confrontare l’OS del Braccio B rispetto al Braccio C in tutti i partecipanti randomizzati. 3) Confrontare la sopravvivenza senza eventi (EFS) del Braccio A rispetto al Braccio C e del Braccio B rispetto al Braccio C in tutti i partecipanti randomizzati. 4) Confrontare la sopravvivenza libera da progressione (PFS) del Braccio A rispetto al Braccio C e del Braccio B rispetto al Braccio C in tutti i partecipanti randomizzati. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Participant has intermediate-stage HCC (hepatocellular carcinoma) whose tumor characteristics exceed the BMU7 criteria and is eligible for TACE
b) Participant has histologic confirmation of HCC
c) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
d) Men and Women must agree to follow methods of contraception
e) Participants are eligible to enroll if they have non-viral related HCC, or if they have HBV-HCC, or HCV-HCC
Other protocol defined inclusion/exclusion criteria could apply. |
a) Participant has intermediate-stage HCC (hepatocellular carcinoma) whose tumor characteristics exceed the BMU7 criteria and is eligible for TACE b) Participant has histologic confirmation of HCC c) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 d) Men and Women must agree to follow methods of contraception e) Participants are eligible to enroll if they have non-viral related HCC, or if they have HBV-HCC, or HCV-HCC
Other protocol defined inclusion/exclusion criteria could apply. |
|
E.4 | Principal exclusion criteria |
a) Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
b) Prior liver transplant or participants who are on the waiting list for liver transplantation
c) Active, known, or suspected autoimmune disease
d) Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
e) Any previous TACE or TAE (trans-arterial embolization without instillation of chemotherapy agent) procedure for HCC
f) Known or suspected allergy to nivolumab, ipilimumab, or study drug components given in association with this trial
Other protocol defined inclusion/exclusion criteria could apply |
a) Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC b) Prior liver transplant or participants who are on the waiting list for liver transplantation c) Active, known, or suspected autoimmune disease d) Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications e) Any previous TACE or TAE (trans-arterial embolization without instillation of chemotherapy agent) procedure for HCC f) Known or suspected allergy to nivolumab, ipilimumab, or study drug components given in association with this trial
Other protocol defined inclusion/exclusion criteria could apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Time to TACE progression (TTTP) will be assessed by the blinded independent central review (BICR): Arm A versus Arm C
2) Overall survival (OS): Arm A versus Arm C |
1) Time to TACE progression (TTTP) will be assessed by the blinded independent central review (BICR): Arm A versus Arm C 2) Overall survival (OS): Arm A versus Arm C |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Time to TACE progression (TTTP) - up to 2 years
2) Overall survival (OS): up to 2.5 years |
1) Time to TACE progression (TTTP) - up to 2 years 2) Overall survival (OS): up to 2.5 years |
|
E.5.2 | Secondary end point(s) |
1) Time to TACE progression (TTTP) will be assessed by the blinded independent central review (BICR): Arm B versus Arm C
2) Overall Survival (OS): Arm B versus Arm C
3) Event-Free Survival (EFS)
4) Progression-free survival (PFS) |
1) Time to TACE progression (TTTP) will be assessed by the blinded independent central review (BICR): Arm B versus Arm C 2) Overall Survival (OS): Arm B versus Arm C 3) Event-Free Survival (EFS) 4) Progression-free survival (PFS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Time to TACE progression (TTTP): up to 2 years
2) Overall Survival (OS): up to 2.5 years
3) Event-Free Survival (EFS): up to 2 years
4) Progression-free survival (PFS): up to 2 years |
1) Time to TACE progression (TTTP): up to 2 years 2) Overall Survival (OS): up to 2.5 years 3) Event-Free Survival (EFS): up to 2 years 4) Progression-free survival (PFS): up to 2 years |
|
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 | 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 |
Biomarker - Immunogenicity |
Biomarcatore - Immunogenicità |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Belarus |
Brazil |
Canada |
China |
Hong Kong |
Japan |
Korea, Republic of |
Puerto Rico |
Russian Federation |
Singapore |
Taiwan |
United States |
Austria |
France |
Germany |
Italy |
Poland |
Spain |
Switzerland |
Czechia |
Argentina |
|
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
|
End of trial is defined as the last participant’s last study visit or scheduled procedure shown in the Schedule of Activities in Protocol (Section 2) for the last participant. |
End of trial is defined as the last participant’s last study visit or scheduled procedure shown in the Schedule of Activities in Protocol (Section 2) for the last participant. |
|
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 | 6 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |