New clinical trial offers hope to patients with glioblastoma

 

It’s aggressive and deadly, and unfortunately, glioblastoma is the most common malignant brain tumor in adults. John McCain was recently diagnosed. Ted Kennedy died from the lethal tumor. But now, an early human clinical trial — the culmination of decades of work — shows a glimmer of hope.

It’s the beginning of the gold nanoparticle synthesis procedure — a bubbling solution of dissolved gold that will soon turn red — a sign nanoparticles, on the order of 10 nanometers, have formed. It’s almost difficult to imagine they are so small.

“There’s a bunch of challenges to delivering that molecule to the right place in a disease setting,” said Andrew Lee, Ph.D., a Northwestern Medicine researcher.

That’s where the nanoparticles shine. Packed with short strands of RNA – poised to deliver a deadly message to cancer cells — the loaded spheres move freely through the bloodstream without notice or reaction. In animal studies, they crossed the protective blood-brain barrier then penetrated tumor cells – ultimately sparking cell death.

“It really is the role of the size of the nanostructure as well as the density and exactly how the molecules are presented by the nanostructure that really give it an advantage in crossing each of those barriers,” Lee said.

We’ve been following this research for years, not just the development of the gold nanoparticle, but also the discovery of a critical gene found in glioblastoma tumors – both advances made by Northwestern Medicine investigators. Finally, the therapy is being tested in humans — from the bench on the campus of Northwestern University, to the bedside at the Lurie Cancer Center.

“It’s particularly exciting to see this technology advance all the way up through pre-clinical work and finally be evaluated for safety in a human trial,” Leesaid.

“We really didn’t think about cancer at all and once the pathology results came back they hit us with this big word we’d never heard … glioblastoma multiforme, and we’re like, ‘What is that?’ I was floored,” said Tahaira Sanders, a glioblastoma patient and study participant.

That was two years ago. Since then Sanders — together with her family and fiance Robert Owens –- have faced the diagnosis with a fighting spirit. Just three weeks ago, she underwent another surgery, this time for a recurrence of her tumor.

“You really want to do your part. You don’t want to have this disease and just have it,” Sanders said.

It’s one of the reasons Sanders decided to take part in the study. The day before her surgery, she received an infusion of the special nanoparticles. After her tumor was removed, the tissue went under the microscope.

“We’re doing testing on the tumor itself to see, did the gold particles reach the tumor?” said Dr. Priya Kumthekar, Northwestern Medicine neuro-oncologist.

It’s called a phase zero study – the purpose is to make sure the compound travels to the tumor and that it’s safe for human consumption.

“This is a targeted, precision approach to having a tumor gently kill itself,” Kumthekar said.

Kumthekar is guiding Tahaira through treatment, which has included chemotherapy and radiation.

“Radiation can help. There are some chemotherapies that are found to be helpful. At some point, the tumor becomes too smart. This means everything to glioblastoma patients if this works. If we could really modify therapy and move the bar to where survival is for these patients,” Kumthekar said.

“I have some faith in it. I really do,” Sanders said.

Sanders is the third patient enrolled in the safety study – doctors hope to infuse three more. If the patients tolerate the treatment, the next step would be to test a higher dose – one that will hopefully kill off tumor cells.

You can learn more about the clinical trial here

And here