A Dose Escalation Study Using Difluoromethylornithine (DFMO) and AMXT-1501 followed by a Randomized Controlled Trial of DFMO with or without AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas
Objective
Phase I Primary Objectives: To evaluate the safety, tolerability and recommended phase 2 dose (RP2D) of AMXT-1501 in combination with continuous infusion DFMO in pediatric and young adult subjects. To determine the recommended Phase II dose.
Phase I Secondary Objectives:To evaluate the activity of AMXT-1501 in combination with DFMO based on: Progression free survival (PFS),Overall response rate (ORR). To evaluate the pharmacokinetics (PK) of AMXT-1501 and DFMO in the blood and CSF.
Phase II Primary Objective: To evaluate, in a prospective randomized clinical trial, the efficacy of difluoromethylornithine (DFMO) in combination with AMXT-1501 compared to DFMO alone in 4 separate disease cohorts based upon Progression Free Survival (PFS): 1. Relapsed/refractory neuroblastoma, 2. Relapsed/refractory ETMR/ATRT: Non-randomized cohort, 3. Diffuse Intrinsic Pontine Glioma (DIPG) at diagnosis after standard of care radiation therapy: Non-randomized cohort, 4. Sarcomas: Relapsed/refractory Ewing Sarcoma and Osteosarcoma: Nonrandomized cohort.
Phase II Secondary Objectives: To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with AMXT-1501 compared to DFMO alone in disease cohorts outlined above, based upon: Overall response rate (ORR), Overall Survival (OS), To evaluate the safety and tolerability profile of difluoromethylornithine (DFMO) in combination with AMXT-1501 in pediatric and young adult subjects.
