E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Specific type of Esophageal cancer called "Esophageal Squamous Cell Carcinoma" (ESCC) that cannot be removed by surgery |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055476 |
E.1.2 | Term | Esophageal squamous cell carcinoma |
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 + dCRT compared with placebo + dCRT in terms of PFS using BICR assessments according to RECIST 1.1 in patients with PD-L1 TAP≥1% tumors |
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E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of PFS using BICR assessments according to RECIST 1.1 in all randomized patients - To assess the efficacy of durvalumab + dCRT compared to placebo + dCRT in terms of OS, APF24, ORR, DoR, DCR, TTP, PFS2, and OS36 in all randomized patients and in patients with PD-L1 TAP≥1% tumors - To assess patient-reported symptoms, functioning, and HRQoL in patients treated with durvalumab + dCRT compared to placebo + dCRT using patient reported outcome measures - To assess the PK of durvalumab when in combination with dCRT in all randomized patients - To investigate the immunogenicity of durvalumab and durvalumab in combination with dCRT in all randomized patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 18 years or older at the time of signing the ICF. • Histologically or cytologically confirmed esophageal squamous cell carcinoma, and present with locally advanced disease (Stage II-IVA). • Unresectable or refusing surgery, and has been deemed suitable for definitive chemoradiation therapy. • Patients with at least an evaluable lesion per RECIST 1.1 • Mandatory provision of available tumor tissue for PD-L1 expression analysis. • ECOG PS 0 or 1. • Adequate organ and marrow function. • Life expectancy of more than 3 months. |
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E.4 | Principal exclusion criteria |
• Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma. • Prior anti-cancer treatment for ESCC. • Patient with a great risk of perforation and massive bleeding. • History of allogeneic organ transplantation. • Active or prior documented autoimmune or inflammatory disorders. • Uncontrolled intercurrent illness. • History of another primary malignancy. • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. • Known allergy or hypersensitivity to any of the study interventions or any of the study interventions excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS using BICR assessments according to RECIST 1.1 in patients with PD-L1 TAP≥1% tumors |
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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 using BICR assessments according to RECIST 1.1 in all randomized patients
- OS, OS36, PFS2 - APF24,ORR, DoR, DCR and TTP per RECIST 1.1 as assessed by BICR in all randomized patients and in patients with PD-L1 TAP≥1% tumors
- Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by EORTC QLQ-C30 and QLQ-OES18 - Concentration of durvalumab in blood - ADA in all randomized patients |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Healthcare resource utilization, Quality of life |
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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 | 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 | 29 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Taiwan |
Brazil |
Canada |
China |
Japan |
Korea, Republic of |
Russian Federation |
Thailand |
United States |
Belgium |
France |
Netherlands |
Poland |
Spain |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial months | 2 |