Please note, this study has closed to accrual and is no longer accepting patients. || This is an open label safety study with an accelerated dose escalation design and early efficacy, single agent, multi institution trial using CED of nal-IRI in children with DIPG following standard of care focal radiotherapy. We will start with a drug concentration of 20 mg/ml and dose escalate up to 40 mg/ml concentration. We will start with a maximum volume of 2 ml of 20 mg/ml (total dose 40 mg) since the total dose of 40 mg has been found to be safe in an ongoing adult study treating adult subjects with recurrent glioblastoma via CED. In our dose escalation scheme we will allow intra-patient dose escalation by first increasing the infusion volume, and then in a second step increasing the concentration to 40 mg/ml followed by a further volume escalation. The concentration of gadoteridol (ProHance) will be 0.5 mM; both agents will be combined and co-infused via the same catheters.

Please note, this study has closed to accrual and is no longer accepting patients. || The overall median survival of children with DIPG is approximately 9 months, and remains unchanged despite decades of clinical trial research. The only standard of care is focal radiotherapy but essentially all children die of this disease. New therapeutic strategies are urgently needed. One of the potential reasons for failure of treatment is the blood-brain and blood-tumor barriers, which exclude potentially effective therapeutic agents. Direct delivery by convection-enhanced techniques can overcome this barrier and ensure adequate drug exposure to tumor cells. Irinotecan has been shown in pre-clinical models to be an effective cytotoxic agent in-vitro and in patient-derived brainstem xenografts, with significantly increased anti-tumor activity when given directly into tumor within the brainstem, compared to systemic delivery. Liposomal encapsulation of irinotecan (nal-IRI) increases the amount of drug that can be delivered, and because of its longer half-life can increase drug exposure over a prolonged period of time. The hypothesis of this study is that repeated direct delivery via convection-enhanced delivery (CED) of nal-IRI will increase progression-free and overall survival in children with newly diagnosed DIPG following standard of care radiotherapy. This trial will assess the safety and preliminary efficacy of this strategy.

PRIMARY OBJECTIVE

To determine the safety and tolerability of repeated administration of nal-IRI co-infused with gadoteridol given by intratumoral CED in children with newly diagnosed DIPG.

SECONDARY OBJECTIVE

To determine the clinical efficacy of repeated administration of nal-IRI given by intratumoral CED in children with newly diagnosed DIPG in the confines of a phase I and early efficacy study.

Funding is provided by The V Foundation.