Researchers preparing to conduct a Phase 3 clinical trial of the mesothelioma drug nintedanib have officially enrolled their first mesothelioma patient. Eventually, close to 400 others will be signed up.
The researchers say they intend to use this study to see how well nintedanib works for patients with unresectable malignant pleural mesothelioma.
They said the enrollees will receive nintedanib in combination with gold-standard mesothelioma chemotherapy drugs pemetrexed and cisplatin.
The mesothelioma patients will continue receiving nintedanib by itself once they complete the chemotherapy regimen, the researchers indicated.
The name of the clinical trial is LUME-Meso. The European health agency responsible for oversight of the trial has assigned it the file number NCT01907100.
The clinical trial will proceed under the auspices of the University of Torino in Italy. Nintedanib is manufactured by pharmaceutical giant Boehringer Ingelheim, headquartered in Germany. Nintedanib is marketed in Europe under the brand name Vargatef®.
Nintedanib is currently unavailable in the U.S. However, Boehringer Ingelheim indicates that it wants to bring it to America, pending the approval of the U.S. Food and Drug Administration.
Mesothelioma Patients Criteria for LUME-Meso Clinical Trial
The researchers in charge of the LUME-Meso clinical trial of nintedanib are looking to enroll patients who meet three criteria.
First, patients cannot have previously undergone surgical resection of their mesothelioma tumors. Also, those tumors now must be so far advanced that surgical resection is no longer clinically feasible.
Second, patients who want to enroll in LUME-Meso cannot have previously undergone chemotherapy or other first-line therapies aimed at knocking down their mesothelioma tumors.
Third, patients in this trial must have a performance status of 0-1. That is a rating based on a formula devised by the Eastern Cooperative Oncology Group.
If qualifying for enrollment, patients in LUME-Meso will find that is a double-blind study. Some of the patients will receive nintedanib plus pemetrexed and cisplatin. Others will receive a matching placebo.
LUME-Meso will not be conducted exclusively at the University of Torino. It is slated to take place at multiple centers across the European continent.
“The primary endpoint of the trial is progression-free survival and overall survival is the key secondary endpoint,” the researchers announced. “Other secondary endpoints include objective tumor response and disease control.”
Drug Targets Mesothelioma Cell Receptors
The researchers said that they will be encouraged if they see no progression of mesothelioma in patients who have taken nintedanib and completed a maximum of six chemotherapy cycles.
Patients whose disease progression stopped will continue to receive nintedanib until one of two events occurs. The first would be the resumption of mesothelioma progression. The second would be the onset of serious side effects that defy control.
Nintedanib works by targeting certain receptors that mesothelioma cells express. The targets are vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and proto-oncogene tyrosine-protein kinase (Src) pathways.
VEGF, FGF, PDGF and Src are targets because they help mesothelioma tumors grow and spread. The idea behind nintedanib is to disrupt VEGF, FGF, PDGF and Src functioning so that the mesothelioma tumors receive no growth support.
Boehringer Ingelheim says that nintedanib is also being evaluated in a separate Phase 3 clinical trial to gauge its effectiveness against advanced colorectal cancer.
In 2014, the European Medical Agency approved nintedanib in combination with docetaxel for treatment of non-small cell lung cancer (NSCLC).