Overview

Diadem to Investigate the Activity and Safety of Durvalumab

Status:
Completed

Trial end date:
2019-05-16

Target enrollment:
0

Participant gender:
All

Summary

Malignant pleural mesothelioma (MPM) is a cancer with high mortality rate and few therapeutic options.essentially all patients usually progress and die subsequently to a first line therapyl. There is strong evidence that the immune system is deeply involved in the biogenesis of MPM and that an imbalance in pro-inflammatory cytokines and exhausted adaptive T-cell mediated immune response are the main causes of neoangiogenesis, progression and metastatisation processes.Numerous Phase II-III clinical trials are underway evaluating Durvalumab either as monotherapy or combination with evidence of activity in a wide range of solid tumors. Durvalumab has received FDA approval as second line treatment in patients with locally advanced or metastatic urothelial carcinoma. Given these prospects for PD-L1 Ab, a Phase II study is proposed in order to evaluate the activity and safety of Durvalumab in advanced pretreated MPM.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Mario Negri Institute for Pharmacological Research

Treatments:

Antibodies, Monoclonal
Durvalumab

Criteria

Inclusion Criteria:

1. Histological diagnosis of advanced unresectable MPM;

2. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (preferred) or at least 5 unstained slides for central determination of PD-L1
expression;

3. Aged ≥ 18 years;

4. Performance status 0-1 (ECOG);

5. Measurable disease as defined by Modified RECIST v1.1 for MPM;

6. One previous chemotherapy line for MPM, based on pemetrexed plus platinum derivative
combination;

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.

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. Any other anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy,
targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
investigational agent);

5. History of primary immunodeficiency;

6. HIV( Ab anti HIV+), active TB infection , HBV or HCV infection;

7. History of allogeneic organ transplant;

8. History of hypersensitivity to durvalumab or any excipient;

9. Any condition that, in the opinion of the investigator, would interfere with study
treatment or patient safety;

10. History of other malignancies (except basal cell carcinoma or cervical carcinoma in
situ, adequately treated, melanoma stage one, prostate adenocarcinoma, bladder
cancer), unless in remission for 3 years or more and judged of negligible potential of
relapse;

11. Unstable cardiac condition, including congestive heart failure or angina pectoris,
myocardial infarction within one year before enrolment, uncontrolled arterial
hypertension or arrhythmias;

12. Brain / leptomeningeal involvement;

13. Any previous treatment with a PD-1 or PD-L1 inhibitor, including Durvalumab;

14. AEs from prior anticancer therapy that have not resolved to grade ≤ 1 except for
alopecia