MRI-Guided, Convection-Enhanced Therapy on Horizon for High-Grade Gliomas

Greg Kennelty

A new treatment delivery method is being explored that combines real-time imaging with convection-enhanced delivery of chemotherapy for patients with high-grade gliomas, according to the lead investigator of early phase research exploring the approach, Nicholas A. Butowski, MD.

Nicholas A. Butowski, MD

A new treatment delivery method is being explored that combines real-time imaging with convection-enhanced delivery of chemotherapy for patients with high-grade gliomas, according to the lead investigator of early phase research exploring the approach, Nicholas A. Butowski, MD.

In a phase I trial, nanoliposomal irinotecan (nal-IRI; MM-398) was safely and effectively delivered to a brain tumor using MRI imaging. According to Butowski, director, Translational Research in Neuro-Oncology, University of California, San Francisco, the real-time time imaging component allows for immediate correction of any mistakes or slight miscalculations and ensures that the cytotoxic agent is hitting the mark.

To gain further insight into this novel treatment delivery strategy,Targeted Oncologyspoke with Butowski, about the feasibility, efficacy, and adverse events seen with this approach.

TARGETED ONCOLOGY:Can you describe your research this novel delivery system?

There was recently a phase I study encompassing something called convection-enhanced delivery of nanoliposomal irinotecan with real-time imaging. In essence, this is real-time delivery of the drug intratumorally through convection-enhanced delivery. So at the same time we are injecting the drug into patients, we are also imaging to make sure that the target is hit. This is also great because you can correct if there are any problems.

This method brings fairly new technology together with this imaging platform in a way that’s really never been done before. Prior studies have used convection-enhanced delivery but they never confirmed whether the target has been hit or not. Imaging is always done after the fact, so this is different because the imaging is being done while the infusion is going on.

This phase I trial is just proving safety thus far, but we are interested in taking it to the next level. This includes making the platform and delivery of the drug much better and more refined, in addition to eventually leading up to multiple injections over time. The other thing we’d like to continue to investigate is reducing the cost of something like this.

TARGETED ONCOLOGY:Are there any toxicities associated with this treatment?

The toxicities relevant to this are that it’s a surgical procedure, so you can have bleeding or infection. Beyond that, there doesn’t seem to be any toxicities as far as the drug itself goes. The drug is well tolerated.

If you gave this systemically through an IV, what would happen is that you would get bad diarrhea, gastrointestinal issues. When you’re injecting it straight into the brain, you’re bypassing systemic administration and you’re bypassing all those side effects. Thus far we haven’t seen any unique issues with delivering a much smaller volume intratumorally.

TARGETED ONCOLOGY:What are the next steps of furthering this treatment?

The next steps would be finishing off the dose escalation portion of the trial. We still have two cohorts to go. The added design challenge of delivering drug name intratumorally is not just having a set volume and trying to figure out if you do a variable volume with a set concentration, since tumors are different shapes and present different challenges when you’re injecting directly into brain.

That’s one thing we need to look into — trying to compensate for that random variable volume of delivery. Then the next step beyond that challenge is figuring out repeated injections over time. This would include looking into if you can cover more volume from the get go, or if you would cover more volume if the patient experiences recurrence and if the drug was effective.

We have seen imaging responses in all of our patients in the areas that we were able to deliver the drug to. The problem is that we are limited by volume at the moment. As we increase volume, we will be able to deliver more drug and have presumably even better response.

Then what we need to do is deliver that over repeated injections over time and hopefully eventually bring this to the pediatric population.

TARGETED ONCOLOGY:What should community oncologists know about this treatment?

The best thing to know is that if you have a patient with a recurrent, high-grade tumor — either grade 3 or grade 4 are eligible for this treatment – refer them to academic center so they can assess whether or not the patient is eligible and if they can receive novel treatment like this. This platform is available at major academic institutions, so checking in with them about a patient to see whether this trial’s treatment is available or if other trials are available.

This is the same genre of the POLIOVIRUS study at Duke, which has gained a lot of press. This convection-enhanced delivery uses the same kind of delivery mechanism, except for the POLIOVIRUS trial, the drug was delivered over an amount of time. It was blind delivery where you make sure the catheter is in the right place, but then you don’t put the patient in the MRI scan to deliver the drug. For the convection-enhanced delivery, you’re left in the scanner for two or three hours and we make sure the drug gets to where it has to go.

It was a prohibitively expensive procedure in the past, so the message here to community oncologists is that the field Is advancing to where that type of treatment has become at least feasible at an academic institution, and hopefully one day beyond that.