Clinical trial: Diadem to Investigate the Activity and Safety of Durvalumab (NCT04115111)

Eligibility 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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 61-year-old man comes to the clinic due to nonproductive cough and progressive dyspnea.  The patient's medical conditions include hypertension, hypercholesteremia and peptic ulcer disease.  He smokes 2 packs of cigarettes daily for the past 30 years.  On examination, there are decreased breath sounds and percussive dullness at the base of the left lung.  Other vital signs are normal. Abdomen is soft without tenderness. CT scan shows a left-sided pleural effusion and nodular thickening of the pleura. The plural fluid was bloody on thoracentesis. Biopsy shows proliferation of epithelioid-type cells with very long microvilli.

Patient description (patient's own words): I am 61 and I had to go to the clinic because I couldn't stop coughing and I experienced some breath shortness. I suffer from hypertension and cholesterol and I also have a stomach ulcer. I should admit that I've been smoking 2 packs of cigarettes every day for the past 30 years. My doctor told me that my breath in my left lung sounds bad. But he told me that my blood pressure, heart rate, breathing rate and temperature are normal. My belly is also normal. However my X-Rays show some liquid on the left side and a mass where the liquid got hard. The scary thing is that the liquid was bloody when they got it out. They did a biopsy and it showed that I have an increase of epithelioid-type cells with very long microvilli.

Does the patient match the trial criteria? 1