NCT04504552: IMPEDE

Immune Checkpoint Inhibitor In High Risk Oral Premalignant Lesions

Status unknown Phase 2 Last updated 1 December 2020

What this trial tests

Phase 2 trial testing Avelumab in Oral Premalignant Lesions in 240 participants. Status unknown.

Timeline

16 July 2020

Primary endpoint
31 October 2023

31 March 2024

Quick facts

Lead sponsor	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	240
Start date	16 July 2020
Primary completion	31 October 2023
Estimated completion	31 March 2024
Sites	5 locations across Italy

Drugs / interventions tested

• Avelumab (avelumab) — full drug profile →

Conditions studied

• Oral Premalignant Lesions — all drugs for Oral Premalignant Lesions →

Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia — full company profile →

Who can join

18 and older, any sex, with Oral Premalignant Lesions. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This trial is designed as a prospective, multi-centre, open-label, single-arm, phase II study.

Oral Premalignant Lesions (OPL) may be considered the equilibrium phase of the immunoediting concept, i.e. a dynamic process between the tumour cells and the immune system including surveillance by the immune system or tumour progression. Thus, an imbalance in immunosuppressive microenvironment is a possible key in malignant transformation. In this regard, the activation of the PD-1/PD-L1 pathway has a central role, witnessed by the expression of PD-L1 by multiple cell types within the microenvironment of OPL (tumour-associated macrophages, fibroblasts, lymphocytes) and by the fact that PD-L1 expression in epithelial and subepithelial cells is associated with malignant transformation. The use of checkpoint inhibitors in this setting seems to be justified by this rationale. Employing intermediate end-point markers during preventive strategies against OPL may allow the conduction of smaller trials, able to give insights for designing larger studies and to better select the population receiving benefit from the treatment. In this regard, the evaluation of phenotypic changes (reduction in size or in grade of dysplasia) may not be enough to assess the potential benefit of an intervention. Modulation of molecular markers may be more precise indicator of oral cancer risk in patients with OPL. Thus, the change in LOH at critical loci may be considered intermediate end-point biomarkers of prevention as well as predictors of cancer risk at baseline. Previous experience with anti-EGFR agents showed the feasibility of such measures in a prevention trial.

Publications & conference data

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

1. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
   Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
2. Overview of Oral Potentially Malignant Disorders: From Risk Factors to Specific Therapies.
   Lorini L, Bescós Atín C, Thavaraj S, Müller-Richter U, et al · · 2021 · cited 49× · PMID 34359597 · DOI 10.3390/cancers13153696
3. Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy.
   He Y, de Araújo Júnior RF, Cruz LJ, Eich C. · · 2021 · cited 48× · PMID 34683963 · DOI 10.3390/pharmaceutics13101670
4. Unmet Needs and Perspectives in Oral Cancer Prevention.
   Bouaoud J, Bossi P, Elkabets M, Schmitz S, et al · · 2022 · cited 28× · PMID 35406587 · DOI 10.3390/cancers14071815
5. Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy.
   Rangel R, Pickering CR, Sikora AG, Spiotto MT. · · 2022 · cited 24× · PMID 35154165 · DOI 10.3389/fimmu.2022.840923
6. Comprehensive Immunoprofiling of High-Risk Oral Proliferative and Localized Leukoplakia.
   Hanna GJ, Villa A, Mistry N, Jia Y, et al · · 2021 · cited 22× · PMID 36860910 · DOI 10.1158/2767-9764.crc-21-0060
7. Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis.
   Deng S, Wang S, Shi X, Zhou H. · · 2022 · cited 15× · PMID 36012205 · DOI 10.3390/ijms23168940
8. Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia.
   Gan CP, Lee BKB, Lau SH, Kallarakkal TG, et al · · 2022 · cited 13× · PMID 36119104 · DOI 10.3389/fimmu.2022.954567