Ipilimumab for Malignant pleural mesothelioma

Inclusion criteria

• {"criterion_text":"- Capable of written informed consent and adherence to study procedures\n- Pathologically confirmed PM (histology: epithelioid), cT2-3 N0-1 M0 according to UICC TNM 9 and considered inoperable by the Multidisciplinary Tumor Board of UZA/UZG at the start of the trial. They only enter the second surgical stage when becoming operable after neoadjuvant therapy\n- Aged 18 years or older\n- World Health Organization (WHO) Performance Status 0-1\n- Fit for systemic chemotherapy, immunotherapy and surgery according to good clinical practice\n- No pregnancy allowed: women of childbearing potential have to take adequate contraception to avoid pregnancy; men need to take adequate contraception to avoid pregnancy in female partners"}

Exclusion criteria

• {"criterion_text":"- Operable PM patients according to TNM 9 criteria (T1) or inoperable PM patients who will not have a chance to become operable after neoadjuvant treatment according to TNM 9 criteria (some T3, all T4, N2-3, M1)\n- Contralateral mediastinal (N2) or distant metastatic disease (evaluated by PET and chest CT)\n- Patients unfit for systemic chemotherapy, immunotherapy or intrathoracic surgery. Patients with an active autoimmune disease or who have had prior splenectomy, an active/acute infection requiring antibiotics, a chronic infection (e.g. HIV, hepatitis B or C) or have a serious cardiac disease are unfit for systemic therapy because their immune system is not properly functioning\n- Hypersensitivity or contraindications to the active substance or to any of the excipients of the medications (platinum salts, pemetrexed, ipilimumab, nivolumab) used in this study\n- Concurrent active malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix\n- Prior treatment with chemotherapy, immunotherapy, surgery (except for diagnostic thoracoscopy) or thoracic RT (including prophylactic tract irradiation)\n- Patients with significantly altered mental status or with psychological, familial, sociological or geographical conditions potential hampering compliance with the study as decided by the investigator"}

Primary endpoints

• {"endpoint_text":"- The rate of success, which is defined as a composite endpoint of feasibility (successful completion of 2 cycles of neoadjuvant immunotherapy and chemotherapy, being selected as operable thereafter and having extended P/D), efficacy (being alive and without signs of progressive disease) and safety (no grade 3-4 residual toxicity from systemic treatment and complete resolution of major complications (grade III - V) according to the Ottawa Classification at week 17+/-2weeks after start of treatment","definition_or_measurement_approach":"Composite endpoint combining feasibility (completion of 2 cycles of neoadjuvant chemo+immunotherapy, subsequent selection as operable and extended P/D surgery), efficacy (alive and without progressive disease) and safety (no grade 3-4 residual systemic toxicity and complete resolution of major complications grade III-V per Ottawa Classification); assessed at week 17 ± 2 weeks after treatment start."}

Secondary endpoints

• {"endpoint_text":"- Toxicity, assessed by CTC-AE scores and by the Ottawa scores for surgery","definition_or_measurement_approach":"Toxicity graded using Common Toxicity Criteria for Adverse Events (CTC-AE) and Ottawa surgical complication scores."}
• {"endpoint_text":"- Efficacy, assessed by the percentage of T2 and T3 PM patients becoming operable after double neoadjuvant chemotherapy and immunotherapy which is defined by the radiology department using the TNM 9 criteria","definition_or_measurement_approach":"Efficacy measured as percentage of T2 and T3 pleural mesothelioma patients converted to operable status by radiology using UICC TNM 9 criteria."}
• {"endpoint_text":"- Pathological response as graded by light microscopy by an experienced pathologist estimating the percentage of viable tumor cells. Less than 10% viable cells will be considered a major pathological response (MPR). Zero % viable cells will be considered pathological complete response (pCR). RECIST protocol: response evaluation criteria in solid tumors.","definition_or_measurement_approach":"Pathological response assessed by histopathology estimating percentage viable tumor cells; MPR defined as <10% viable cells; pCR defined as 0% viable cells. Radiologic response per RECIST where applicable."}
• {"endpoint_text":"- Progression-free survival (PFS), measured from the date of registration until any progression","definition_or_measurement_approach":"PFS measured from registration date until documented progression."}
• {"endpoint_text":"- Overall survival (OS), measured from the date of registration until death or last available follow-up","definition_or_measurement_approach":"OS measured from registration date until death or last follow-up."}
• {"endpoint_text":"- Local disease-free survival (DFS), measured from the date of registration until local progression","definition_or_measurement_approach":"Local DFS measured from registration until local disease progression."}
• {"endpoint_text":"- Quality of life, assessed by the EQ-5D-5L score","definition_or_measurement_approach":"Quality of life measured using the EQ-5D-5L instrument."}

Belgium

Earliest CTIS Part Ii Submission Date

22-02-2025

Latest Decision Or Authorization Date

11-03-2025

Processing Time Days

17

Number Of Sites

2

Number Of Participants

37

Primary sponsor

Full Name

Antwerp University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium