Nintedanib as Switch Maintenance Treatment of Pleural Malignant Mesothelioma

• Status: Unknown status
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, randomized, 1:1, double blinded phase II trial. Patients with unresectable malignant pleural mesothelioma (MPM) will be randomized between arm A: nintedanib and arm B:placebo

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Treatments: Nintedanib

Criteria

Inclusion Criteria:

• Histological diagnosis of unresectable Malignant Pleural Mesothelioma (MPM);

• Response or Stable disease according to modified RECIST criteria [48] after first line platinum-pemetrexed chemotherapy for 4-6 cycles;

• Last platinum chemotherapy dose administered within 60 days (i.e. randomization must occur within 60 days from the last dose of the last cycle of platinum-pemetrexed chemotherapy);

• Age >18 years;

• ECOG performance status (PS) 0-2;

• Life expectancy of at least 12 weeks in the opinion of the investigator;

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose

Exclusion Criteria:

• prior systemic anticancer therapy including cytotoxic therapy or immune-checkpoint inhibitor, for MPM, other than first line platinum-based doublet chemotherapy;

• previous extra-pleural pneumonectomy (other forms of previous surgery eg pleurectomy are acceptable);

• previous Vascular Endothelial Growth Factor (VEGF) inhibitors (eg bevacizumab, sorafenib, etc);

• treatment with other investigational drugs or treatment in another clinical interventional trial within the past 4 weeks before start of therapy or concomitantly with the trial;

• patients that, in the opinion of the investigator, have reduced performance status by 2 ECOG levels (e.g. PS 0 to 2 or PS 1 to 3) from beginning to completion of 1st line chemotherapy;

• radiotherapy (with the exception of palliative radiotherapy) during study or within 4 weeks of start of study drug;

• known brain metastasis or lepto-meningeal disease. Patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasisNo active brain metastases (e.g. stable for < 4 weeks;, no adequate previous treatment with radiotherapy;, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization); patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to assess brain metastasis;

• leptomeningeal metastases;

• significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial;

• pre-existing clinically significant ascites and/or clinically significant pleural effusion;

• active or history of bleeding complications that would prevent anti-angiogenic therapy

• centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels; typical mediastinal pleural involvement with mesothelioma remains eligible;

• clinically active cancer other than mesothelioma within 5 years prior to start of study treatment;

• radiographic evidence of cavitatory or necrotic tumors;

• unstoppable use of therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =325mg per day);

• clinically significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive New York Heart Association (NYHA) II, serious cardiac arrhythmia, clinically significant pericardial effusion)