A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery

PRIMARY OBJECTIVES: I. To estimate the 2-year progression-free survival (PFS) rate in patients with progressive, surgically unresectable desmoid tumor treated with nirogacestat. II. To describe the toxicities of nirogacestat in children and adolescents with desmoid tumor. III. To characterize the pharmacokinetics (PK) of nirogacestat in children and adolescents. SECONDARY OBJECTIVE: I. To determine the objective tumor response rate (ORR) of nirogacestat in children and adolescents with progressive, surgically unresectable desmoid tumor. EXPLORATORY OBJECTIVES: I. 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. II. To explore the effect of nirogacestat on immune cells and immunoglobulin levels in the peripheral blood. III. To collect blood samples for banking at baseline, during treatment, and at the time of progression for future research. IV. To compare assessment of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO) criteria, and T2 and volumetric changes using magnetic resonance imaging (MRI). V. To utilize a tool developed to specifically assess patient reported outcomes (PROs) in adult patients with desmoid tumor (GOunder/DTRF DEsmoid Symptom/Impact Scale \[GODDESS\]) and the Patient Reported Outcomes Measurement Information System (PROMIS) to explore the relationship between PROs and tumor response and PFS. OUTLINE: Patients receive nirogacestat orally (PO) twice daily (BID) on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) and computed tomography (CT) or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study. After completion of study treatment, patients are followed up at 30 days.