In a new trial, Sunnybrook researchers are exploring the use of focused ultrasound (FUS) to open the blood brain barrier (BBB) and enhance the delivery of chemotherapy to glioblastoma (GBM).
GBM is the most common and aggressive cancerous primary brain tumour (a tumour that starts in the brain). These tumours are made up of different cell types, the most common being astrocytes (a star-shaped glial cell of the nervous system). GBMs are usually highly cancerous because the cells reproduce quickly and have a large network of blood vessels supporting them.
Lead researcher Dr. Nir Lipsman explains the challenges of treating GBM and what he hopes the trial will accomplish:
What is this focused ultrasound trial looking at?
We are investigating focused ultrasound as a novel strategy for the delivery of chemotherapy to GBM. We use a helmet-like device, containing over 1,000 individual transducers (which convert electrical energy into sound energy), to converge ultrasound waves on to discrete points in the brain. The idea is to temporarily open the BBB to allow the passage of chemotherapy to regions surrounding the tumour.
What is the blood brain barrier?
The BBB is a physical barrier that protects the brain. It’s invisible to the naked eye – and made up of cells that work together to prevent toxins from getting passed the barrier and into the brain. In many ways, that’s a good thing because it stops dangerous things from reaching our brains. But, it also stops medications like chemotherapy from reaching tumours, where they are needed most. (Find out how focused ultrasound opens the blood brain barrier here.
How does this focused ultrasound trial work?
We recently completed and published a phase 1 feasibility study, where we looked at whether opening the BBB using FUS was safe, reversible and well tolerated by GBM patients. We found that it was.
For this phase 2 trial, patients will undergo the current standard of care for GBM: Surgery to remove as much of the tumour as possible, followed by radiation and chemotherapy. Patients then go on to “maintenance chemotherapy” with a drug called temozolomide with the hope of stopping the cancer’s return or growth. Temozolomide came onto the scene about 15 years ago and is able to pass through the BBB with some effectiveness. But, could it do even better if the BBB is open?
Our trial participants will take temozolomide, which is an oral pill, about an hour before we open the BBB with FUS. We target the ultrasound waves to the rim of the tumour, and the BBB is then open for several hours, while the drug circulates throughout the body and brain. The procedure takes about 3-4 hours in total, and most patients go home the same day, or the next morning.
Trial participants (so far we have recruited five) will have a total of six chemotherapy treatments together with FUS BBB opening. We are especially interested in whether opening the BBB repeatedly, over several months, is safe and well-tolerated by patients, and whether there is any effect on tumour growth or progression.
Why do you have to add to this to the current standard of care instead of just trying this new way?
A standard of care is in place because it works, so we cannot interfere with a potentially effective treatment, even as we investigate others. The challenge for us as researchers is to find a way to explore and investigate a new treatment, to demonstrate that it is safe and promising, while not influencing the standard treatment for a given disease. If we can, however, show that something has real potential, we can challenge the standard of care by comparing the new method to the standard to see if one produces better results.
Why is GBM so hard to treat?
GBMs are highly heterogeneous tumours — two patients with a GBM can have different molecular and genetic profiles. Even within one person’s tumour, the molecular profile can vary. That makes it very difficult to find a one-size-fits-all approach in terms of chemotherapy, in addition to the challenge of getting past the blood brain barrier.
GBM is also often diagnosed at a later stage, when cells have already begun to move to other parts of the brain, and spread beyond what is visible on an MRI.
What’s next?
If we show that repeated FUS BBB opening together with temozolomide is safe and well tolerated, our plan is to expand the trial to more patients, and perhaps include other centres in Canada.
In addition, we’d like to see whether there would be benefit to moving FUS to upfront treatment, at diagnosis, or perhaps when patients have a recurrence. We will also start looking at other chemotherapy drugs, whether those that are currently available or new formulations, or perhaps some that don’t cross the BBB at all that might be even better for GBM.
What do you hope this means for patients?
GBM is one of the most challenging conditions we treat in neurosurgery. Our hope is that trials like this brings us closer to effective treatments that will change the course of the disease.
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What does it take to run a trial like this?
We are uniquely positioned at Sunnybrook to conduct FUS in brain cancer. We have globally recognized experts in oncology, medical physics and neurosurgery, all laser-focused on developing new therapies. This trial wouldn’t be possible without a small army of clinicians, researchers, coordinators and students, the work of Kullervo Hynynen at SRI, and close collaboration with the oncology teams of Drs. James Perry and Arjun Sahgal at Odette Cancer Centre. Most important are the patients themselves, who volunteer to take part, and who inspire us on a daily basis to push forward with this work.
For more information or to inquire about eligibility for the trial, please contact Maheleth Llinas at harquailcentre@sunnybrook.ca
Learn more about oncology trials at Sunnybrook’s Harquail Centre for Neuromodulation
