Fenretinide (4-Hpr)/Lym-X-Sorb (Lxs) Oral Powder Plus Ketoconazole In Patients With High-Risk (Hr) Recurrent Or Resistant Neuroblastoma: A New Approach To Neuroblastoma Therapy (Nant) Consortium Trial.

10071 Background: Fenretinide (4-HPR), a cytotoxic retinoid with preclinical activity in neuroblastoma (NB), formulated as 4-HPR/LXS oral powder increased plasma levels over a capsule formulation but exhibited a PK plateau at higher doses (Pediatr Blood Cancer 60:1801, 2013). Two expansion cohorts were undertaken to assess effects on 4-HPR plasma levels of: 1) removing dietary restrictions, 2) adding ketoconazole, an inhibitor of 4-HPR metabolism. Methods: Eligible patients had high-risk NB with recurrent or refractory disease, including in complete response (CR) after relapse (Cohort One-only). Treatment in Cohort One was 4-HPR at 1500 mg/m2/day, divided TID, given on Days 1-7, every 3 weeks, with an unrestricted diet. In Cohort Two, concurrent oral ketoconazole (6 mg/kg/day) was given on Days 1-7. Results: Cohort One accrued 23 patients (3 not treated) with 15 eligible for PK analysis; Cohort Two accrued 22 patients, with 16 eligible for PK analysis (3 too early). There were no Course 1 DLT’s. Grade 3 t...