Clinical and histological evidence of Oral Premalignant Lesions (OPL) with high risk of malignant transformation MedDRA version: 20.0 Level: PT Classification code 10078906 Term: Oral soft tissue biopsy System Organ Class: 10022891 - Investigations
Conditions
Interventions
Product Name: avelumab
Product Code: [MSB0010718C]
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 1537032-82-8
Current Sponsor code: MSB0010718C
Other descriptive name: trade n
Sponsors
AZIENDA SOCIO SANITARIA TERRITORIALE DEGLI SPEDALI CIVILI DI BRESCIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent; 2. Male or female > 18 years of age; 3. ECOG Performance status (PS) 0-1(see Appendix 2); 4. 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 - see Appendix 3). These conditions define “LOH positivity”; 5. OPL with a histological definition of dysplasia and a minimum diameter of at least 20 mm; 6. Be willing to provide tissue from newly obtained oral biopsies; 7. 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); 8. Adequate bone marrow function: neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, haemoglobin > 9 g/dL; 9. Adequate liver function: bilirubin 60 mL/min; 11. If of childbearing potential, willingness to use effective contraceptive method (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. 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); 2. Oral lesions due to lichen planus; 3. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness; 4. Any test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection; 5. 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); 6. Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV (see Appendix 4), uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months; 7. Significant neurologic or psychiatric disorders including dementia or seizures; 8. Active uncontrolled infection (requiring IV antibiotics) or active tuberculosis; 9. Active disseminated intravascular coagulation; 10. Other serious underlying medical conditions which could impair the ability of the patient to participate into the study; 11. Having participated in another clinical trial or having received any investigational agent in the preceding 30 days before study entry; 12. Known allergic/hypersensitivity reaction to any of the components of the treatment; 13. Pregnancy (absence confirmed by serum/urine beta HCG) or breastfeeding; 14. Other active malignancy within 3 years, with the exception of a history of a previous, adequately treated: - basal cell carcinoma of the skin - pre-invasive carcinoma of the cervix - superficial bladder cancer - carcinoma in situ of the prostate, cervix or breast, - head and neck carcinoma surgically treated (radiotherapy treatment not allowed); 15. Legal incapacity or limited legal capacity; 16. Medical, psychological or socio-geographical condition or situation which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent; 17. Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to be enrolled; 18. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of study drug administration. Inhaled or topical steroids, steroids as premedication for hypersensitivity reactions and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To revert the risk of malignant transformation of OPL through a short course of immunotherapy with avelumab. This objective will be evaluated both in its final endpoint (malignant transformation) and with an intermediate endpoint (reversal of loss of heterozygosity -LOH- status);Secondary Objective: •To evaluate the safety of immunotherapeutic approach in OPL •To assess the change of histological grade of OPL •To discover genomic and imaging predictive tools able to foresee response to avelumab;Primary end point(s): 1.To revert the risk of malignant transformation of OPL through a short course of immunotherapy with avelumab. This objective will be evaluated both in its final endpoint (malignant transformation) and with an intermediate endpoint (reversal of loss of heterozygosity -LOH- status) 2.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;Timepoint(s) of evaluation of this end point: 1.6 months after the start of treatment 2. 6 months after the start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Grade 3-5 adverse events or any treatment interruption due to toxicities (safety) • Change of histological grading of OPL • Identification of multi-omic signatures associated with response to immunotherapy;Timepoint(s) of evaluation of this end point: continuosly 6 months 6 months and at malignant transformation | — |
Countries
Italy
Contacts
Public ContactCRO
Clinical Research Technology
Outcome results
None listed