Andrew Brenner, M.D., leads a brand new first-in-human clinical trial to fight Glioblastoma.

Tiny fat particles deliver big radiation

Wednesday, April 1, 2015by Elizabeth Allen

Glioblastomas are the deadliest of brain tumors, and researchers at the CTRC have found a new way to target them with nanotechnology. Neuro-oncologist Andrew Brenner is leading the first ever trial to use this new technology in patients.

The idea: tiny radioactive fat particles, only 100 nanometers across, inserted by the thinnest of catheters directly into a tumor, where they remain, radiating only a tiny distance, affecting only the tumor.

The target: the deadliest of brain tumors, called glioblastomas.

The concept was developed at the UT Health Science Center by nuclear medicine physician William T. Phillips, M.D., and biochemist Beth A. Goins, Ph.D., in the Department of Radiology; and Ande Bao, Ph.D., a medical physicist and pharmaceutical chemist formerly in the Department of Otolaryngology, all of the Long School of Medicine at UT Health San Antonio . They originally thought of trying it in head and neck cancers.

But Andrew Brenner, M.D., Ph.D., a neuro-oncologist at the UT Health San Antonio MD Anderson Cancer Center, had a different vision.

“I thought it made sense to use it in brain cancer first,” Dr. Brenner said. “The skull is a rigid structure” and the tissue inside is much less varied, he said, whereas in the neck and other parts of the head there are many different kinds of tissue and lots of moving parts.

Fast-moving and difficult to treat

While not all brain tumors are malignant, the glioblastoma is especially deadly. Moreover, as the tumor advances it affects the brain in unpredictable ways, often involving radical shifts in personality and behavior.

“It’s a terrible thing for a family to lose a loved one to glioblastoma,” Dr. Brenner said. “It’s tough to lose them to any cancer, but with the brain tumor you see them change right before your eyes.”

The best technology for treatment, radiation, has not changed much in 40 years, he said. And those beams of radiation must cut through healthy tissue to reach their target. The nanotechnology is igniting hope that we will soon have a major step forward in treatment options for brain cancer, and there is potential that it could also be adapted for use in other cancers.

A mountain of work before the first human experiment

Working with Drs. Phillips, Goins and Bao, Dr. Brenner began moving the research forward. That involved a dizzying array of tasks: getting funding, designing experiments that showed initial success, leading to the work of getting more funding for more experiments.

Each success led to more work at higher levels, until Dr. Brenner was setting up the collaboration with the nanotechnology characterization lab at the National Cancer Institute. He sent the national lab the procedures and samples and they analyzed them. The results were solid, and led to an investigational new drug (IND) application with the FDA (involving a protocol and investigator brochure, teleconferences and submission of data and yet more data).

Separately, the CTRC Foundation collaborated with the UT Health Science Center to create a company, NanoTx Therapeutics, which could access funding to push the research forward faster than the academic machine normally does. Working with NanoTx, Dr. Brenner wrote business and scientific proposals, gaining a $2 million grant from the Cancer Prevention and Research Institute of Texas in February.

The excitement was brewing, and subsequent news coverage of the grant meant people whose family members had a glioblastoma contacted the CTRC, eager to see about participating in the first clinical trial to be done in humans. On March 10, Dr. Brenner worked with neurosurgeon John R. Floyd II, M.D., to apply the first treatment to David Williams at University Hospital.

“One of the challenges is how to get the highly radioactive nano liposomes into the brain, and precisely into the tumor,” Dr. Floyd said. “Surgical targeting, precision and delivery became of the utmost importance.”

In the past, using a catheter to apply traditional chemotherapy has run into problems because of the catheter design, he said. “To effectively deliver this novel therapy, and improve our surgical targeting, we would need a better catheter. The one we are using is a new design, enabling us to deliver small quantities in precise locations. We are very pleased already with delivery in our first case.”

A note of caution

It can be hard to explain to desperate family members that not everybody is eligible for a study, and that the study is just that – not a guarantee of cure.

“You never know until you begin the studies how a human being is going to react to a new therapy, and we have to be very careful about how we proceed on that,” Dr. Brenner said. And in this case it’s not only the therapy that’s new, it’s how it gets to the tumor.

“The main limitation right now is that we have to start with small-sized tumors, until we get a better handle on our delivery methods, to make sure we can cover larger tumors,” he said.

Caution is the word on new therapies in general – that’s why they go through such an enormous vetting process before they ever get to the first willing patient.

But Dr. Brenner has a good feeling about this one.

“I don’t like to oversell an unproven drug,” he said, “but I would like to say the laboratory results were very encouraging. I have evaluated a lot of therapeutics and I have not seen this level of efficacy before.”