NCT03472274: DUTRENEO

Durvalumab (MEDI4736) and TREmelimumab in NEOadjuvant Bladder Cancer Patients (DUTRENEO)

Completed Phase 2 Last updated 13 April 2023

What this trial tests

Phase 2 trial testing Durvalumab in Bladder Cancer in 101 participants. Completed in 12 April 2023.

Timeline

25 October 2018

Primary endpoint
30 April 2021

12 April 2023

Quick facts

Lead sponsor	Fundacion CRIS de Investigación para Vencer el Cáncer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	101
Start date	25 October 2018
Primary completion	30 April 2021
Estimated completion	12 April 2023
Sites	11 locations across Spain

Drugs / interventions tested

• Durvalumab — full drug profile →
• Tremelimumab (TREMELIMUMAB) — full drug profile →
• Cisplatin-based neoadjuvant chemotherapy

Conditions studied

• Bladder Cancer — all drugs for Bladder Cancer →

Sponsor

Fundacion CRIS de Investigación para Vencer el Cáncer — full company profile →

Who can join

18 and older, any sex, with Bladder Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

In the treatment of localized/locally advanced urothelial cancer, there are several questions that have not yet been resolved, such as the limited benefit of cisplatin-based chemotherapy in the adjuvant or neoadjuvant context, the difficulty in establishing which groups actually benefit from either perioperative treatment and what are the molecular markers that could help us predict the response to this treatment to allow a better selection of patients. On the other hand, not all patients are candidates for cisplatin-based chemotherapy and carboplatin is not comparable in activity, so there is an urgent need to find other drugs that may offer a therapeutic opportunity to these patients.

In the context of metastatic disease, immunotherapy has been able to modify the natural history of this disease, administered as monotherapy, but the combination with double immune checkpoint inhibitors is also being evaluated with promising results. Even this therapeutic strategy is being advanced to the context of adjuvant and neoadjuvant treatment of urothelial tumors. In this sense, on the one hand, the present study, as a research in the neoadjuvant setting, constitutes the opportunity to define molecular phenotypes in bladder cancer since the design of this study will allow both, to evaluate the efficacy of the drug when the tumor is operable and to carry out an extensive analysis of biomarkers in the tumor tissue of these patients with an in-vivo evaluation of immune-based therapy activity. On the other hand, it allows to evaluate a strategy of double-immune checkpoint inhibitors that has already demonstrated activity in metastatic disease and, taking into account, the modest benefit of standard chemotherapy in the perioperative context: platinum-based neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) Modest increase in overall survival, but only a subset of eligible patients are eligible to receive it. In addition, radical cystectomy alone, in MIBC patients, presents a 5-year relapse rate of 10-50%.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.
   Bellmunt J, Hussain M, Gschwend JE, Albers P, et al · · 2021 · cited 322× · PMID 33721560 · DOI 10.1016/s1470-2045(21)00004-8
2. Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives.
   Roviello G, Catalano M, Santi R, Palmieri VE, et al · · 2021 · cited 44× · PMID 34503220 · DOI 10.3390/cancers13174411
3. Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review.
   Barone B, Calogero A, Scafuri L, Ferro M, et al · · 2022 · cited 43× · PMID 35626149 · DOI 10.3390/cancers14102545
4. Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer.
   de Jong FC, Rutten VC, Zuiverloon TCM, Theodorescu D. · · 2021 · cited 40× · PMID 33802033 · DOI 10.3390/ijms22062800
5. Neoadjuvant immunotherapy and chemoimmunotherapy for stage II-III muscle invasive bladder cancer.
   Chen H, Yang W, Xue X, Li Y, et al · · 2022 · cited 26× · PMID 36059550 · DOI 10.3389/fimmu.2022.986359
6. Advanced Bladder Cancer: Changing the Treatment Landscape.
   Bilim V, Kuroki H, Shirono Y, Murata M, et al · · 2022 · cited 25× · PMID 36294884 · DOI 10.3390/jpm12101745
7. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of urothelial cancer.
   Galsky MD, Balar AV, Black PC, Campbell MT, et al · · 2021 · cited 25× · PMID 34266883 · DOI 10.1136/jitc-2021-002552
8. PD‑1/PD‑L1 immune checkpoint inhibitors in neoadjuvant therapy for solid tumors (Review).
   Tang Q, Zhao S, Zhou N, He J, et al · · 2023 · cited 19× · PMID 36866750 · DOI 10.3892/ijo.2023.5497