The Dr. Souweidane’s Phase 1 Trial Findings

Findings
From April 5, 2012, to Oct 8, 2016, 28 children were enrolled and treated in the trial, of whom 25 were evaluable for the primary endpoint. The maximum tolerated dose was not reached as no dose-limiting toxicities were observed. One (4%) of 28 patients had treatment-related transient grade 3 hemiparesis and one (4%) had grade 3 skin infection. No treatment-related grade 4 adverse events or deaths occurred. Estimated volumes of distribution (Vd) were linearly dependent on volumes of infusion (Vi) and ranged from 1・5 to 20・1 cm3, with a mean Vd/Vi ratio of 3・4 (SD 1・2). The mean lesion absorbed dose was 0・39 Gy/MBq 12⁴I (SD 0・20). Systemic exposure was negligible, with an average lesion-to-whole body ratio of radiation absorbed dose higher than 1200.

Interpretation 
Convection-enhanced delivery in the brainstem of children with diffuse intrinsic pontine glioma who have previously received radiation therapy seems to be a rational and safe therapeutic strategy. PET-based dosimetry of the radiolabelled antibody [12⁴I]-8H9 validated the principle of using convection-enhanced delivery in the brain to achieve high intra-lesional dosing with negligible systemic exposure. This therapeutic strategy warrants further development for children with diffuse intrinsic pontine glioma.

Dr. Souweidane mentioned that the trial is about hope. It is about admitting that we have been failing the children for decades. Finally, quoted below is what he wrote on his blog to answer the question “How do you feel about the outcome of the research?”

I can’t tell you how many people have asked me that recently, now that we have published the culmination of years and years of work. Embodied in the results of my Phase I clinical trial are multiple grants, kind donations, unending lab projects, thousands of emails, meeting presentations, many sleepless nights, and so much time away from my own family and two young boys. I’m not sure how to answer: I’m equal parts overjoyed, proud, exhausted – and overwhelmed by the thought my quest is not finished. I have never felt more optimistic, and I find myself at the threshold of something very meaningful. Mostly I’m feeling determined to keep going, to get to the next level, and to get my hands on a real cure for this killer.

Read Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial