LUME-Meso: Double blind, randomised, multicentre, phase II/III study of nintedanib in combination with pemetrexed / cisplatin followed by continuing nintedanib monotherapy versus placebo in combination with pemetrexed / cisplatin followed by continuing placebo monotherapy for the treatment of patients with unresectable malignant pleural mesothelioma

Most people who have unresectable mesothelioma die from their disease en new
treatments are therefore necessary. Chemotherapy is standard therapy for
mesothelioma, but interrupting the angiogenesis of tumors opens new
possibilities for the improvement of the treatment.
Proteins involved in regulating the angiogenic process as vascular endothelial
growth factor (VEGF) and platelet-derived growth factor (PDGF) have been
implicated in the prognosis of mesothelioma.
Nintedanib is a triple kinase inhibitor targeting VEGFR, PDGFR and FGFR
(fibroblast growth factor receptor). Based on the available preclinical and
clinical data, nintedanib displays a manageable safety profile and signal of
efficacy in various tumour types.
Please refer also to section 1.1 of the clinical trial protocol

To evaluate the safety and efficacy in terms of progression-free survival (PFS)
and overall survival (OS) of nintedanib + pemetrexed / cisplatin followed by
nintedanib versus placebo + pemetrexed / cisplatin followed by placebo as first
line treatment for patients with unresectable malignant pleural mesothelioma
(MPM). (also refer to section 2.1 and 2.2 of the clinical trial protocol)

This is a randomized, double-blind, placebo-controlled, multicenter phase 3
study. Globally 450 patients will be included and 15 in the Netherlands.
50% of the patients will be randomized and treated with nintedanib and 50% of
the patients will be randomized and treated with nintedanib matching placebo
(1:1 randomization)
(Please also refer to section 3.1 and 3.2 of the clnical trial protocol)

Nintedanib or matching placebo will be administered in combination with
standard pemetrexed and cisplatin for a maximum of 6 cycles of a 21-day cycle.
For patients who have not progressed, nintedanib or matching placebo will
continue to be administered orally on a daily basis until disease progression,
unmanageable toxicity, withdrawal of consent or death.

Patients will spend approximately 40 hours at the hospital in a year time;
consisting of 30 visits.

Patients will require somewhat more imaging than they receive regular care.
Patients will be exposed to more radiation than standard of care and patients
may experience side effects from nintedanib (and of pem/cis).

At every visit blood will be drawn and the patient will need to fill in 2
questionnaires.
Approximately 285 ml blood will be drawn in a year time. This includes the
optional sampels.

Patients will receive a physical examination more often than usual.