Clinical study to investigate the activity and safety of anti-PD-L1 antibody (Durvalumab) in patients with advanced malignant pleural mesothelioma after a previous therapy

Phase 1

• Conditions: Advanced malignant pleural mesothelioma; MedDRA version: 20.0Level: PTClassification code 10027406Term: MesotheliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000617-67-IT
• Lead Sponsor: IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-02
• Last Update Posted: 15 October 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

1.Cytological or histological diagnosis of
unresectable MPM (advanced or inoperable);
2.Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides for central determination of PD-L1 expression;
3.Aged = 18 years;
4.Performance status 0-2 (ECOG);
5.Measurable disease as defined by Modified RECIST v1.1 for MPM;
6.One previous chemotherapy line for MPM of pemetrexed plus platinum derivative;
7.Previous chemotherapy course concluded at least 4 weeks prior to recruitment;
8.Signed informed consent;
9.Negative pregnancy test. All patients in reproductive age or potential must agree to use effective contraception, as defined by the study protocol for the entire duration of treatment with study drug and for 3 months following its interruption;
10.Patients who have received palliative radiation are eligible if <30% of bone marrow was irradiated and normal hematological function was completely regained;
11.Adequate organ and marrow function as defined below: Haemoglobin = 9.0 g/dL, Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3), Platelet count = 100 x 109/L (>100,000 per mm3);
12.Adequate liver function: Serum bilirubin = 1.5 x institutional upper limit of normal (ULN) (except for patients confirmed Gilbert’s syndrome, who will be allowed only in consultation with their physician); AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be = 5x ULN;
13.Adequate renal function: Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.

Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria:
1.Radiotherapy with curative intent to thoracic wall (concomitant with or prior to chemotherapy);
2.Severe concomitant illness;
3.History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis;
4.Enrolment in other trials;
5.Any other anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent);
6.Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis);
7.History of primary immunodeficiency;
8.HIV, TB, HBV or HCV infection (HBsAg+; HCV-RNA+);
9.History of allogeneic organ transplant;
10.History of hypersensitivity to durvalumab or any excipient;
11.Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving Durvalumab;
12.Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results;
13.History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 years or more and judged of negligible potential of relapse;
14.Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias;
15.Brain / leptomeningeal involvement;
16.Any previous treatment with a PD-1 or PD-L1 inhibitor, including Durvalumab;
17.Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
18.AEs from prior anticancer therapy that have not resolved to grade = 1 except for alopecia

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of antiPD-L1 Ab Durvalumab in patients with MPM relapsing after first line treatment with pemetrexed plus platinum-based drugs.;Secondary Objective: -Progression Free Survival (PFS)<br>-Overall survival (OS)<br>-Objective Response rate (ORR)<br>-Safety<br>-Exploratory: PD-L1 IHC expression in tumour samples and tumour infiltrating lymphocytes (TIL).<br>;Primary end point(s): Proportion of patients alive and free from progression or death at 16 weeks (PFS 16 w) calculated from the start of treatment (Durvalumab).;Timepoint(s) of evaluation of this end point: 16 weeks from the start of Durvalumab administration