Novel Drug for Glioblastoma Bombs in Phase 3 Trial

Zosia Chustecka

February 28, 2013

A large phase 3 study of the investigational integrin inhibitor cilengitide (under development by Merck KgaA, Germany) for glioblastoma has bombed.

This is the most advanced product being explored for the treatment of glioblastoma. It was thought to have considerable potential because integrin inhibition has been shown to result in antiangiogenic, direct antitumor, and anti-invasion activity.

The phase 3 study, known as CENTRIC, was conducted in 500 patients from 23 countries.

The addition of cilengitide to the standard treatment of temozolomide plus radiotherapy did not improve overall survival, according to the company. A spokesperson said that "the results are disappointing," but added that no new or unexpected safety concerns were noted.

"The results illustrate how challenging this disease remains," said lead investigator Roger Stupp, MD, head of neuro-oncology in the Department of Neurosurgery at the University of Lausanne Medical Center in Switzerland.

The patients in this trial had newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter status.

Another trial (the phase 2 CORE study) of cilengitide is still ongoing, but is being conducted in patients with unmethylated MGMT gene promoter status.

Complete results from CENTRIC will be presented at the American Society of Clinical Oncology annual meeting in June, according to the company.

In other glioblastoma news, a large trial of the novel headset with electrodes, known as NovoTTF (Novocure), is underway. This device, which is worn on a shaved scalp, produces electrical fields around the tumor to inhibit cancer cell growth. It was approved by the US Food and Drug Administration in 2011 for adults with glioblastoma who had progressed after chemotherapy.

In the NovoTTF trial, patients with newly diagnosed glioblastoma who have completed standard of care with surgery and chemoradiation (with temozolamide) are being treated with the device. The researchers intend to enroll 700 patients at 40 centers, and expect the trial to run for 2 years.