It will be four years in May since Dr. Souweidane treated the very first patient in his clinical trial testing the safety of convection-enhanced delivery (CED) of 124I-8H9 against DIPG. (The 8H9 antibody has been shown to bind to the tumor, and 124I kills cancer cells with radiation.) The trial was originally expected to last for two years and treat12 DIPG patients at four dose levels; in 2014 the FDA approved an extension of the trial to seven dose levels. Dr. Souweidane is currently treating patients at the seventh dose level, and has re-treated several children. There have been no adverse effects on any child.
Unlike standard IV or oral chemotherapy, CED delivers the agent directly to the tumor and does not pass through the kidneys, liver, or other organs the drug might damage. It also gets more of the drug directly to the tumor, since it’s not blocked by the protective blood-brain barrier. The CED method has been shown to achieve more than 1,000 times the concentration of the drug in the tumor site than other chemotherapy, without the toxicity of other delivery methods.
“Each treatment is a marathon for everyone,” says Dr. Souweidane. “We typically begin at 7:30 in the morning and often don’t finish until 3 or 4 am the following day. That’s not only tough on the OR team, but it’s also hard on the waiting family. But with each and every child treated we learn something new, and I’m extremely encouraged by the results so far.”
Dr. Souweidane now has extensive data on how the agent penetrated each tumor, what concentrations were achieved, and how long the drug stayed in the tumor. Once the final dose level is complete, Dr. Souweidane expects to move the trial to a multi-site model, in which patients across the country can be treated without having to travel to New York. Not only will more children be treated, but the trial can proceed to the phase in which it is tested for effectiveness and not just safety. Testing other agents, at different dosages, will provide an enormous amount of new data for researchers to plumb for answers.