RARE-32. Phase 0 and feasibility single-institution clinical trial of intravenous tocilizumab for adamantinomatous craniopharyngioma

Abstract

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control. METHODS: Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado. The phase I stratum involves IV tocilizumab prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥30kg or 12 mg/kg for patients who weigh <30kg. RESULTS: To date, three patients have been enrolled on the Phase 0 component of the trial. These patients demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and/or tumor tissue, compared to undetectable levels in control samples. Two patients (1 male and 1 female; median age 10.5 years) have enrolled on the feasibility stratum; one patient had best response of minor response but met definition of progressive disease at cycle 11. One patient with extensive disease required dose reduction for myelosuppression. CONCLUSION: Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is planned through a CONNECT consortium international Phase II trial.