E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically (or radiologically for patients undergoing curative ablation) confirmed Hepatocellular Carcinoma (HCC), newly diagnosed, and successfully completed curative therapy (resection or ablation). |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077746 |
E.1.2 | Term | Hepatocellular carcinoma stage I |
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 |
To assess the efficacy of durvalumab in combination with bevacizumab compared to placebo in terms of Recurrence-free survival (RFS) |
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E.2.2 | Secondary objectives of the trial |
Arm A: Durvalumab + bevacizumab Arm B: Durvalumab + placebo Arm C: Placebo
-To compare the efficacy of Arm B versus Arm C in terms of RFS -To assess the efficacy of Arm A vs Arm C and Arm B vs Arm C in terms of other efficacy endpoints (i.e. RFS24, RFS36, TTR, RFS2/PFS2, OS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation) 2.Imaging to confirm disease-free status within 28 days prior to randomization 3.ECOG 0-1 at enrolment 4.Child-Pugh score of 5 or 6 5.Patients with HBV infection must receive antiviral therapy at least after enrollment per institutional practice to ensure adequate viral suppression prior to randomization. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. 6.Patients with HCV infection must be managed per local institutional practice for the study and for 6 months after the last dose of study treatment. 7.Adequate organ and marrow function, as defined by the CSP |
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E.4 | Principal exclusion criteria |
1.Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC 2.Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging 3.History of hepatic encephalopathy within 12 months prior to randomization 4.Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging 5.Patients with Vp1 to Vp4 portal vein thrombosis on baseline Imaging are excluded 6.Active co-infection with HBV and HDV. 7.Receipt of prior systemic anticancer therapy for HCC 8.Those on a waiting list for liver transplantation |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments for RFS will be collected regularly at predefined time points until disease recurrence or death |
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E.5.2 | Secondary end point(s) |
Overall survival (OS) Time to recurrence (TTR) RFS at 24 months (RFS24) and RFS at 36 months (RFS36) Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments will be made regularly until disease recurrence, death, or until the end of the study |
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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 | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Peru |
Hong Kong |
Taiwan |
Australia |
Brazil |
Canada |
China |
Japan |
Korea, Republic of |
Thailand |
United States |
Austria |
France |
Germany |
Italy |
Türkiye |
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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
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Last expected visit/contact of last patient undergoing the study |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |