E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically or cytologically documented muscle-invasive transitional cell carcinoma (TCC) of the bladder |
|
E.1.1.1 | Medical condition in easily understood language |
Muscle Invasive Bladder Cancer (T2-T4a, N0-1) in stage II and IIIA without lymph node involvement |
|
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 | PT |
E.1.2 | Classification code | 10005010 |
E.1.2 | Term | Bladder cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005011 |
E.1.2 | Term | Bladder cancer stage III |
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 assess efficacy of investigational product in patients with MIBC using pCR and EFS |
|
E.2.2 | Secondary objectives of the trial |
To assess efficacy and safety of investigational product in patients with MIBC using the following:
EFS, pCR, EFS24
Proportion of patients who achieve <P2
Proportion of subjects with cystectomy
Metastasis-free survival and disease-specific survival
OS
OS at 5 years
DFS2
PFS2
Pharmacokinetic and Immunogenicity
Safety and tolerability profile |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Germany biomarker sub-study (A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer (NIAGARA)) Date and version: Local CSP Germany (Version 2.0) to Global Amendment 2 (Version 3), 03-Jan-2020 Objectives: To investigate the predictive and prognostic value of compositional elements of the MIBC tumor immune microenvironment at baseline and at cystectomy; to investigate the impact and dynamics of intrinsic subtypes and mutational profiles of MIBC with the tumor microenvironment, at baseline and at cystectomy |
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E.3 | Principal inclusion criteria |
Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology;
Patients must be planning to undergo a radical cystectomy at the time of randomization;
Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
ECOG performance status of 0 or 1 at enrollment.
Availability of tumor sample prior to study entry;
Must have a life expectancy of at least 12 weeks at randomization. |
|
E.4 | Principal exclusion criteria |
Evidence of lymph node (N2-N3) involvement or metastatic disease at the time of screening.
Contra-indication to any of the study drugs
Requires immunosuppression medication for a concomitant condition
Active or prior documented autoimmune or inflammatory disorders |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 6 months (pCR) Up to 48 months (EFS) |
|
E.5.2 | Secondary end point(s) |
EFS, pCR, EFS24
Proportion of patients who achieve <P2
Proportion of subjects with cystectomy
Metastasis-free survival and disease-specific survival
PFS2
OS
OS at 5 years
DFS
Pharmacokinetic and Immunogenicity
Safety and tolerability profile |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 6 months (pCR; Proportion of patients who achieve <P2) Up to 24 months (EFS24) Up to 60 months (OS5) Up to 84 months (OS; PFS2, DFS, Safety and tolerability profile) Up to 48 months (Other endpoints) |
|
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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 |
Chile |
Philippines |
Taiwan |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Turkey |
United Kingdom |
United States |
Viet Nam |
Belgium |
Czechia |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
|
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
|
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 9 |