CTNI-05. USE OF SUBCUTANEOUS PROGESTERONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA

Abstract PURPOSE/BACKGROUND Glioblastomas (GBMs) are aggressive primary brain tumors that invariably fail therapy highlighting need for better treatments. While high dose progesterone displayed anti-GBM activity, currently available formulations of progesterone cannot achieve these high levels on a daily basis. Subcutaneous progesterone has been approved in Europe for pregnancy support and can potentially achieve the drug levels needed. A phase 1 trial to assess feasibility, tolerability and efficacy of subcutaneous progesterone for recurrent GBM was initiated but closed early due to slow accrual. Here, we report our experience with this cohort. METHOD Study was approved/overseen by the Emory IRB and Winship DSMC. Subcutaneous progesterone was provided by Institut Biochimique SA (Lugano, Switzerland). GBM patients at 1st-3rd recurrence were eligible. A 3 + 3 design was utilized with dose limiting toxicities (DLTs) determined after 4 weeks. Treatment was maintained until intolerable toxicity or tumor progression up to 24 weeks. Serum pharmacokinetics (PKs) were assessed early in therapy course. Brain MRIs were performed pre-treatment and at 4, 8, 16 and 24 weeks while patients remained on study. RESULTS At study closure, 4 patients had enrolled. All were male and between 32-78 years of age, 3 enrolled at dose level 0 (50 mg/day) and 1 enrolled at dose level 1 (75 mg/day) without development of DLTs. PK assessment showed high serum levels in the expected range. Patients were taken off study after 4 (N=2), 16 (N=1) and 24 (N=1) weeks of therapy due to tumor progression with one displaying an objective tumor response on MRI at 16 weeks. No ≥ grade 3 adverse events at least possibly due to this therapy were noted. CONCLUSION For recurrent GBM patients, daily subcutaneous progesterone appeared safe/tolerable, achieved high serum levels and produced an objective response. More study is necessary to determine viability of this salvage therapy.