The effect of corticorelin acetate on peritumoral brain edema: An interim report of an open-label study as part of a phase III program

Abstract

9095 Background: Steroid treatment of peritumoral brain edema (PBE) in patients with malignant brain tumors (BTs) is frequently associated with debilitating steroid side effects. The investigational agent corticorelin acetate injection, a synthetic peptide identical to h-corticotropin-releasing factor (hCRF), compared favorably to dexamethasone in reducing PBE in animal models of primary or metastatic BT. Toxicology and clinical studies including a pilot study in patients with malignant BTs published in ASCO's Annual Meeting Proceedings, showed hCRF to be safe and virtually devoid of steroid side effects. Methods: Following completion of follow-up periods for one of 2 randomized, double-blind phase III trials comparing corticorelin acetate to placebo or dexamethasone, patients with primary or metastatic BTs, PBE on pre-randomized study MRIs, and Karnofsky Performance Scores =50 were enrolled in an open-label extension study in which they took 1.0 mg corticorelin acetate by subcutaneous injection bid. We tapered dexamethasone maximally as tolerated. Patients were assessed every 4 weeks. Results: Of 47 patients who received open-label corticorelin acetate for up to one year, 28 patients continue to take it. Corticorelin acetate was safe and well tolerated, with no related deaths or SAEs. Patients typically refractory to reducing steroids - including at least 5 patients >55 years of age, 7 patients with recurrent brain tumor, and 11 patients in whom prior attempt(s) to reduce dexamethasone had been unsuccessful – reduced dexamethasone with improvement or resolution of steroid side effects. We will present data in the first 30 patients to take corticorelin acetate for at least 12 weeks [the largest and longest-treated group reported to date] including changes in steroid side effects correlated with net cumulative changes in dexamethasone, and treatment-emergent AEs. Conclusions: This interim analysis supports corticorelin acetate's long-term safety, tolerability, and steroid-sparing potential. The outcome of the ongoing randomized trials may determine whether this innovative agent leads to fundamental changes in the management of PBE in patients with primary or metastatic BTs. [Table: see text]