A Safety, Pharmacokinetic and Efficacy Study of a ;-Secretase Inhibitor, Nirogacestat (PF-03084014; IND# 146375), in Children and Adolescents with Progressive, Surgically Unresectable Desmoid Tumors
Objective
Primary Aims To estimate the 2-year progression-free survival (PFS) rate in patients with progressive, surgically unresectable desmoid tumor treated with nirogacestat. To describe the toxicities of nirogacestat in children and adolescents with desmoid tumor. To characterize the pharmacokinetics (PK) of nirogacestat in children and adolescents.
Secondary Aims To determine the objective tumor response rate (ORR) of nirogacestat in children and adolescents with progressive, surgically unresectable desmoid tumor.
Exploratory Aims To collect blood, archival tumor samples and on-study/post-treatment tumor samples (if available) from patients enrolled on this trial to correlate various CTNNB1 and APC gene mutations and genomic signatures with tumor response and PFS. To explore the effect of nirogacestat on immune cells and immunoglobulin levels in the peripheral blood. To collect blood samples for banking at baseline, during treatment, and at the time of progression for future research. To compare assessment of tumor response using RECIST, WHO criteria, and T2 and volumetric changes using MRI. To utilize a tool developed to specifically assess patient reported outcomes (PROs) in adult patients with desmoid tumor (GODDESS) and the Patient Reported Outcomes Measurement Information System (PROMIS) to explore the relationship between PROs and tumor response and PFS.
