Diadem to Investigate the Activity and Safety of Durvalumab

NCT04115111 | Completed Phase 2

• 1 other identifier: IRFMN-MPM-7109
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pleura Mesothelioma

Keywords

malignant pleural mesothelioma

Outcome Measures

Primary Outcomes (1)

• Proportion of survived patients at 16 weeks

  Proportion of patients alive and free from progression or death at 16 weeks (PFS 16 w) calculated from the start of treatment (Durvalumab).

  16 weeks

Secondary Outcomes (6)

• Progression free survival

  16 weeks

• overall survival

  16 weeks

• Objective response rate

  16 weeks

• Tumour growth index

  16 weeks

• Evidence of Number of Adverse Events

  16 weeks

Study Arms (1)

Durvalumab arm

EXPERIMENTAL

Patients will receive Durvalumab at the dose and regimens described above every 4 weeks until evidence of disease progression or occurrence of unacceptable toxicity. Patients who show evidence of disease progression but appear to tolerate Durvalumab well, for whom no other treatment options exist and who, at the judgement of the investigator, may still enjoy clinical benefit, will be classified as failures and offered the possibility to continue treatment with extended follow up.

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab in monotherapy as second line treatment

Durvalumab arm

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of advanced unresectable MPM;
• 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;
• Aged ≥ 18 years;
• Performance status 0-1 (ECOG);
• Measurable disease as defined by Modified RECIST v1.1 for MPM;
• One previous chemotherapy line for MPM, based on pemetrexed plus platinum derivative combination;
• Previous chemotherapy course concluded at least 4 weeks prior to recruitment;
• Signed informed consent;
• 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;
• Patients who have received palliative radiation are eligible if \<30% of bone marrow was irradiated and normal hematological function was completely regained;
• 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);
• 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;
• 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.

You may not qualify if:

• Radiotherapy with curative intent to thoracic wall (concomitant with or prior to chemotherapy);
• Severe concomitant illness;
• 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;
• Any other anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent);
• History of primary immunodeficiency;
• HIV( Ab anti HIV+), active TB infection , HBV or HCV infection;
• History of allogeneic organ transplant;
• History of hypersensitivity to durvalumab or any excipient;
• Any condition that, in the opinion of the investigator, would interfere with study treatment or patient safety;
• 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;
• Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias;
• Brain / leptomeningeal involvement;
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including Durvalumab;
• AEs from prior anticancer therapy that have not resolved to grade ≤ 1 except for alopecia

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

San Gerardo Hospital

Monza, 20133, Italy

Location

Related Publications (1)

• Canova S, Ceresoli GL, Grosso F, Zucali PA, Gelsomino F, Pasello G, Mencoboni M, Rulli E, Galli F, De Simone I, Carlucci L, De Angelis A, Belletti M, Bonomi M, D'Aveni A, Perrino M, Bono F, Cortinovis DL; DIADEM groupD. Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma. ESMO Open. 2022 Dec;7(6):100644. doi: 10.1016/j.esmoop.2022.100644. Epub 2022 Dec 1.

  PMID: 36463732 RESULT

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Diego Cortinovis, MD

  ASST-Monza San Gerardo Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 3, 2019
• Study Start: October 17, 2018
• Primary Completion: May 16, 2019
• Study Completion: May 16, 2019
• Last Updated: March 15, 2023

Record last verified: 2023-03

Locations

IT (1)