Abstract Brain tumors are the top cause of cancer death in pediatric patients. Two with highest mortality are relapsed, or refractory, HGG (including DMG) or ATRT (rHGG/rATRT). Iron plays a key role in many tumors’ essential cellular processes. HGG cells have transport proteins that preferentially take up ferric iron iron (III) via transferrin receptors (TfRs) to drive cellular proliferation. Gallium is a metal in the same period as iron, and so similar to transferrin-bound iron (III) that it is taken into the cell via TfRs, acting as a “Trojan horse” to disrupt essential tumor processes, causing cell death. Gallium maltolate (GaM) is a compound stable in solution and orally bioavailable. As previously described, our work with pediatric HGG and ATRT cell lines showed, when compared to controls, decreased oxygen consumption and increased apoptosis with GaM treatment; animals with ATRT and HGG xenografts treated with oral GaM had significantly higher median overall survival, and these tumors grew at a significantly slower rate. The animals also had excellent maintenance of quality of life observing behaviors such as social activity and appetite. In our ongoing Phase 1 trial of oral GaM for adult patients with recurrent glioblastoma, GaM has been well-tolerated without significant side effects. Thus, we hypothesize GaM can be safely administered enterally to pediatric patients. This is a prospective, single-arm, open-label phase 1 study to determine safety, tolerance, and pharmacokinetic data of an enteral formulation of GaM in pediatric patients with rHGG or rATRT. Aims: i. Determine the maximum-tolerated and recommended phase 2 dose of GaM, ii. Determine the safety/tolerability of GaM, iii. Describe anti-tumor effect, and iv. Obtain quality of life data. We believe GaM offers a new type of therapy with potential to improve dismal outcomes, while being less burdensome compared to most currently-used rHGG/rATRT regimens.
Rumler et al. (Fri,) studied this question.