NCT03950362: PREVERT

Bladder PREserVation by RadioTherapy and Immunotherapy in BCG Unresponsive Non-muscle Invasive Bladder Cancer

Status unknown Phase 2 Last updated 16 May 2019

What this trial tests

Phase 2 trial testing Avelumab in Non-muscle-invasive Bladder Cancer in 67 participants. Status unknown.

Timeline

15 June 2020

Primary endpoint
15 June 2023

15 June 2024

Quick facts

Lead sponsor	Institut Paoli-Calmettes
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	67
Start date	15 June 2020
Primary completion	15 June 2023
Estimated completion	15 June 2024

Drugs / interventions tested

• Avelumab (avelumab) — full drug profile →
• Radiotherapy — full drug profile →

Conditions studied

• Non-muscle-invasive Bladder Cancer — all drugs for Non-muscle-invasive Bladder Cancer →

Sponsor

Institut Paoli-Calmettes — full company profile →

Who can join

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

Sponsor's own description

About two-thirds of newly diagnosed cases of bladder cancer are non-muscle-invasive bladder cancer (NMIBC). It is advocated that patients with high-risk NMIBC receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG. Radical cystectomy remains the treatment of choice for NMIBC who have failed intravesical therapy, but there are situations when surgery is not feasible due to competing co-morbidities or a patient's desire for bladder preservation. For these patients, the potential options available are limited.

In MIBC, radiotherapy (RT) in association with chemotherapy, has been shown to produce 10-year overall survival rates comparable to those of radical cystectomy in selected cases. At the opposite, results from trials assessing radiotherapy with or without chemotherapy in patients with NMIBC are less documented and discordant.

Immunotherapy with immune-checkpoint blockade therapies is increasing as an option and has shown very promising results for several cancers, including bladder carcinoma.

An established body of published work has shown that radiation enhances many of the steps needed for the generation of antigen-specific immune responses, including inflammatory tumor-cell death, dendritic cell activation, and antigen cross-presentation. Several groups have reported improved local control when checkpoint blockade immunotherapy is added to radiation in different tumor types. On the one hand, radiotherapy might stimulate the induction of local endogenous immune responses by anti-PD-1 treatment. On the other hand, active immune stimulation by anti-PD-1 treatment within the tumor microenvironment might maximize radiation-induced antitumor immunity.

Combination immunoradiotherapy using PD-1/PD-L1 signaling blockade could therefore offer an interesting strategy in bladder tumors, especially as an optional bladder preservation treatment for BCG unresponsive NMIBC.

The originality of the therapeutic strategy is the use of radiation (local treatment) combined with checkpoint blockade immunotherapy (systemic treatment). Radiotherapy might increase response rates by creating a more permissive tumor microenvironment through increasing PD-L1 expression on tumor cells and stimulating the accumulation and activation of CD8+ T cells.

Avelumab seems to have a specific cytotoxic activity suggesting its interest in local control of the disease, especially in association with radiotherapy.

Publications & conference data

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

1. 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
2. New Perspectives in the Medical Treatment of Non-Muscle-Invasive Bladder Cancer: Immune Checkpoint Inhibitors and Beyond.
   Audisio A, Buttigliero C, Delcuratolo MD, Parlagreco E, et al · · 2022 · cited 28× · PMID 35159167 · DOI 10.3390/cells11030357
3. Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer.
   Hannouneh ZA, Hijazi A, Alsaleem AA, Hami S, et al · · 2023 · cited 26× · PMID 38037752 · DOI 10.1002/cam4.6768
4. Immunotherapy Combined With Radiation Therapy for Genitourinary Malignancies.
   Ukleja J, Kusaka E, Miyamoto DT. · · 2021 · cited 24× · PMID 34041029 · DOI 10.3389/fonc.2021.663852
5. From Interferon to Checkpoint Inhibition Therapy-A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette-Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC).
   Deininger S, Törzsök P, Mitterberger M, Pallauf M, et al · · 2022 · cited 18× · PMID 35158964 · DOI 10.3390/cancers14030694
6. Emerging treatments for bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer.
   Kim HS, Seo HK. · · 2021 · cited 18× · PMID 34085791 · DOI 10.4111/icu.20200602
7. Recent Advances in Drug Delivery Strategies for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Brief Review from 2018 to 2024.
   Qu F, Darji S, Thompson DH. · · 2024 · cited 11× · PMID 39339191 · DOI 10.3390/pharmaceutics16091154
8. Real-world treatment patterns and clinical outcomes of Japanese patients with non-muscle invasive bladder cancer receiving intravesical bacillus Calmette-Guérin treatment.
   Miyake M, Kikuchi E, Shinozaki K, Piao Y, et al · · 2022 · cited 8× · PMID 35598101 · DOI 10.1111/iju.14933