Difluoromethylornithine (DFMO) and AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas
NCT Number: NCT06465199
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Atypical Teratoid/Rhabdoid Tumor|Neuroblastoma Recurrent|Embryonal Tumor With Multilayered Rosettes|DIPG Brain Tumor|Ewing Sarcoma|Osteosarcoma Recurrent
Interventions: DRUG: Difluoromethylornithine (DFMO)|DRUG: AMXT-1501 Dicaprate
Sponsor: Milton S. Hershey Medical Center
Collaborators: Aminex Therapeutics, Inc.
Sex: ALL
Age: CHILD, ADULT
Enrollment: 253
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2034-07

Summary:
The purpose of this study is to evaluate the investigational drug AMXT 1501 (a pill taken by mouth) in combination with the drug difluoromethylornithine (DFMO) for infusion administered intravenously (IV; a liquid that continuously goes into your body through a tube that has been placed during a surgery into one of your veins). An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.

The goals of this part of the study are:

* Establish a recommended dose of AMXT 1501 in combination with DFMO for infusion
* Test the safety and tolerability of AMXT 1501 in combination with DFMO for infusion in patients with cancer
* To determine the activity of study treatments chosen based on:
* How each subject responds to the study treatment
* How long a subject lives without their disease returning/progressing

Primary Outcome Measures: Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability, 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., 28 days|Phase II- Number of participants with progression free survival (PFS) during study, 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
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: Non-randomized cohort, 2 years plus 5 years follow up
Secondary Outcome Measures: Phase I- Number of participants with progression free survival (PFS) during study, To evaluate the activity of AMXT-1501 in combination with DFMO based on Progression free survival (PFS), 2 years plus 5 years follow up|Phase I- Determine the Overall Response Rate (ORR) of Participants using INSS Response, To evaluate the activity of AMXT-1501 in combination with DFMO based on Overall response rate (ORR), 2 years|Phase II- Determine the Overall Response Rate (ORR) of Participants using INSS Response, 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), 2 years|Phase II- Length of time that participants experience Overall Survival (OS), To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with AMXT-1501 compared to DFMO alone in disease cohorts outlined above, based upon Overall Survival (OS), 2 years plus 5 years follow up|Phase II-Number of Participants with Adverse Events as a Measure of Safety and Tolerability, To evaluate the safety and tolerability profile of difluoromethylornithine (DFMO) in combination with AMXT-1501 in pediatric and young adult subjects., 2 years plus 30 days