Immune Checkpoint Inhibitor In High Risk Oral Premalignant Lesions

NCT04504552 | Unknown Phase 2

• 1 other identifier: IMPEDE
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Oral Premalignant Lesions

Outcome Measures

Primary Outcomes (2)

• Recurrence-free survival or malignant transformation-free survival

  Recurrence or malignancy-free survival since immunotherapy start, for which the events of interest are the recurrence of OPL with LOH or malignant transformation of OPL

  Every 2 weeks for the first 6 months, then every month for 1 year, then every 3 months for 30 months

• Change in LOH status (positive to negative) of OPL

  Change in LOH status (positive to negative) of OPL after 6 months since the start of immunotherapy. This is defined as disappearance of any high-risk LOH (and the nonappearance of any other high-risk LOH) in the site of the OPL at the histological sample after immunotherapy treatment

  6 months

Secondary Outcomes (3)

• Safety of immunotherapy in the treatment of OPL

  Through study completion, an average of 5 years

• Grading of OPL

  6 months

• Multi-omic signatures

  6 months and through study completion, an average of 5 years

Study Arms (1)

Single Arm Avelumab

EXPERIMENTAL

Avelumab monotherapy on the Day 1 (± 2 days) of a 2-week treatment cycle for 4 administrations.

Drug: Avelumab

Interventions

Avelumab DRUG

Subjects will receive treatment with avelumab monotherapy 800 mg as a 60-minute IV infusion on the Day 1 (± 2 days) of a 2-week treatment cycle for 4 administrations.

Also known as: Bavencio

Single Arm Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent;
• Male or female \> 18 years of age;
• ECOG Performance status (PS) 0-1;
• Clinical and histological evidence of OPL with high risk of malignant transformation as defined by LOH at 3p14 and/or 9p21 plus at least at one additional chromosomal site (4q, 8p,11p,13q, or 17p) or patients with a prior oral cancer history and LOH at 3p14 and/or 9p21 (LOH defined according to EPOC trial). These conditions define "LOH positivity";
• OPL with a histological definition of dysplasia and a minimum diameter of at least 20 mm;
• Be willing to provide tissue from newly obtained oral biopsies;
• Not receiving chronic systemic steroidal therapy or any immunosuppressive therapy within 7 days prior to the first treatment; absence of active autoimmune disease that required systemic treatment in the past 2 years, except the following:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication);
• Adequate bone marrow function: neutrophils \> 1.5 x 109/L, platelets \> 100 x 109/L, haemoglobin \> 9 g/dL;
• Adequate liver function: bilirubin \< 2 X upper normal limit (except known medical reason not interfering with liver function, such as Gilbert disease), SGOT, SGPT, AP, GGT \< 3 x ULN;
• Adequate renal function: calculated or analysed creatinine clearance \> 60 mL/min;
• If of childbearing potential, willingness to use effective contraceptive method (Pearl Index \< 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), sterilization, sexual abstinence for the study duration and 2 months post-dosing.

You may not qualify if:

• Previous immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint receptors);
• Oral lesions due to lichen planus;
• Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness;
• Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection;
• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for the administration of inactivated vaccines (for example, inactivated influenza vaccines);
• Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months;
• Significant neurologic or psychiatric disorders including dementia or seizures;
• Active uncontrolled infection (requiring IV antibiotics) or active tuberculosis;
• Active disseminated intravascular coagulation;
• Other serious underlying medical conditions which could impair the ability of the patient to participate into the study;
• Having participated in another clinical trial or having received any investigational agent in the preceding 30 days before study entry;
• Known allergic/hypersensitivity reaction to any of the components of the treatment;
• Pregnancy (absence confirmed by serum/urine beta HCG) or breastfeeding;
• Other active malignancy within 3 years, with the exception of a history of a previous, adequately treated:
• basal cell carcinoma of the skin

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (5)

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS

Candiolo, Torino, 10060, Italy

NOT YET RECRUITING

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

IRCSS Ospedale Policlinico San Martino

Genova, 16132, Italy

NOT YET RECRUITING

Istituto europeo di oncologia

Milan, 20141, Italy

NOT YET RECRUITING

Istituto nazionale dei tumori Regina Elena

Roma, 00144, Italy

NOT YET RECRUITING

Related Publications (1)

• Gurizzan C, Lorini L, Paderno A, Tomasoni M, Zigliani G, Bozzola A, Ardighieri L, Battocchio S, Bignotti E, Ravaggi A, Romani C, De Cecco L, Serafini MS, Miceli R, Bardellini E, Majorana A, Piazza C, Bossi P. Immunotherapy for the prevention of high-risk oral disorders malignant transformation: the IMPEDE trial. BMC Cancer. 2021 May 17;21(1):561. doi: 10.1186/s12885-021-08297-3.

  PMID: 34001010 DERIVED

MeSH Terms

Interventions

avelumab

Central Study Contacts

Paolo Bossi

CONTACT

+390303996536; paolo.bossi@unibs.it

Mariarita Arenella

CONTACT

+39 089 301545; mariarita.arenella@cr-technology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 7, 2020
• Study Start: July 16, 2020
• Primary Completion: October 31, 2023
• Study Completion: March 31, 2024
• Last Updated: December 1, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 12 months after the end of the trial, for at least 1 year
• Access Criteria: NS

Locations

IT (5)