Eflornithine + AMXT 1501 for Neuroblastoma

Overseen By BCC Enroll

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Uncontrolled infection, BSA <0.25 m2, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

289 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a combination of two oral drugs, AMXT 1501 (AMXT 1501 Dicaprate) and DFMO (Eflornithine), to determine a safe and effective dose for treating neuroblastoma and similar cancers. Researchers aim to evaluate how well these drugs work together to prevent the disease from recurring or worsening. Individuals with relapsed or hard-to-treat neuroblastoma, a cancer affecting nerve cells, may qualify if they have tried other treatments and still have active or stable disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking any current anti-cancer medications to participate in this trial. The trial requires that participants are not currently receiving other anti-cancer agents.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Recent research has studied the safety of combining AMXT 1501 and DFMO. This combination proved to be safe and well-tolerated, with no unexpected safety issues. The recommended dose was determined from these studies, indicating the treatment was effective with manageable side effects. While these findings are reassuring, ongoing research aims to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Eflornithine (DFMO) with AMXT 1501 for treating neuroblastoma because it offers a novel approach compared to existing therapies. Most current treatments for neuroblastoma focus on chemotherapy, radiation, or surgery. However, AMXT 1501, combined with DFMO, targets polyamine metabolism, a unique mechanism that may disrupt cancer cell growth more effectively. This combination could potentially lead to improved outcomes by attacking cancer cells differently than traditional methods.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that the combination of AMXT 1501 and DFMO holds promise against cancer. In animal studies, this combination effectively targeted neuroblastoma, a cancer primarily affecting children. Participants in this trial may receive either AMXT 1501 combined with DFMO or DFMO alone, depending on the treatment arm. The FDA has granted this combination "orphan drug" status, indicating its potential for treating rare conditions like neuroblastoma. Although further research in humans is necessary, these early results offer encouragement for those considering this treatment option. ^{1 2 3 5 6}

Who Is on the Research Team?

Giselle Saulnier Sholler, MD

Principal Investigator

Penn State Health Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young people up to 21 years old with specific cancers like Neuroblastoma, Ewing Sarcoma, and certain brain tumors. It's open to those who have relapsed or haven't responded to other treatments. There are different age groups for the study phases, and it includes newly diagnosed cases of a rare brain cancer called DIPG.

Inclusion Criteria

I have been newly diagnosed with DIPG based on scans.

I was diagnosed at 21 years old or younger.

I am 12 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive up to twenty-four 28-day cycles of AMXT 1501 combined with DFMO in a dose escalation study to establish safety and tolerability

24 months

Phase II Treatment

Participants are randomized to receive either AMXT 1501 with DFMO or DFMO alone, with up to twenty-four 28-day cycles to evaluate efficacy based on progression-free survival

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on progression-free survival and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• AMXT 1501 Dicaprate
• Eflornithine (DFMO)

Trial Overview The trial tests AMXT 1501 combined with DFMO, both oral drugs not yet approved by the FDA. The study aims to find the right dose, check safety and tolerability, and see how well these drugs work in stopping disease progression or return.

How Is the Trial Designed?

Group I: Phase II- Arm A: AMXT 1501 + DFMO Experimental Treatment 2 Interventions

In this portion of the study, cohort 1 will be randomized to either receive Arm A: oral AMXT 1501 at the recommended phase 2 dose (RP2D) found in the Phase I along with oral DFMO at the RP2D found in the Phase I on each day of study or Arm B: oral DFMO alone at the recommended phase 2 dose (RP2D) found in the Phase I. Subjects will receive up to twenty-four (24), 28-day cycles of their assigned treatment. Cohorts 2 (ETMR/ATRT), 3 (DIPG), and 4 (Sarcomas) will automatically be assigned to Arm A with AMXT 1501 in combination with DFMO. Subjects in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Group II: Phase I- Pediatric Cohort Experimental Treatment 2 Interventions

The second phase I will be a pediatric cohort that will be for subjects \< 12 years of age at enrollment in a standard 3+3 design in which groups of 3 subjects per cohort will be treated and assessed. Subjects will receive up to twenty-four (24), 28-day cycles of AMXT 1501 combined with DFMO. Subjects will receive oral AMXT 1501 at a starting dose of 350 mg/m2 BID each day. The dose escalation scheme for subsequent groups and modifications for dose limiting toxicities (DLT) are detailed in the protocol.

Group III: Phase I- AYA Cohort Experimental Treatment 2 Interventions

The initial phase I will be an AYA (adolescents and young adult) cohort that will be for subjects ≥12 years of age at enrollment in a standard 3+3 design in which groups of 3 subjects per cohort will be treated and assessed. Subjects will receive up to twenty-four (24), 28-day cycles of AMXT 1501 combined with DFMO. Subjects will receive oral AMXT 1501 at a starting dose of 350 mg/m2 BID each day. The dose escalation scheme for subsequent groups and modifications for dose limiting toxicities (DLT) are detailed in the protocol.

Group IV: Phase II- Arm B: DFMO Alone Active Control 1 Intervention

In this portion of the study, cohort 1 will be randomized to either receive Arm A: oral AMXT 1501 at the recommended phase 2 dose (RP2D) found in the Phase I along with oral DFMO at the RP2D found in the Phase I on each day of study or Arm B: oral DFMO alone at the recommended phase 2 dose (RP2D) found in the Phase I. Subjects will receive up to twenty-four (24), 28-day cycles of their assigned treatment. Cohorts 2 (ETMR/ATRT), 3 (DIPG), and 4 (Sarcomas) will automatically be assigned to Arm A with AMXT 1501 in combination with DFMO. Subjects in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Aminex Therapeutics, Inc.

Industry Sponsor

Trials

4

Recruited

320+

Penn State University

Collaborator

Trials

380

Recruited

131,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06465199

NCT06465199 | Eflornithine (DFMO) and AMXT 1501 for ... The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is ...

2. esmoopen.com esmoopen.com/article/S2059-7029(25)01445-0/fulltext

Phase I dose-escalation trial of AMXT 1501 dicaprate plus ... In the most recent studies, AMXT 1501 plus DFMO showed pronounced anticancer activity in the transgenic mouse models of tyrosine hydroxylase MYC ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2059702925014450

Phase I dose-escalation trial of AMXT 1501 dicaprate plus ... In the most recent studies, AMXT 1501 plus DFMO showed pronounced anticancer activity in the transgenic mouse models of tyrosine hydroxylase MYC neuroblastoma ( ...

4. onclive.com onclive.com/view/amxt-1501-plus-difluoromethylornithine-nets-fda-orphan-drug-designation-in-neuroblastoma

AMXT 1501 Plus Difluoromethylornithine Nets FDA ... A phase 1/2 trial will assess the combination's efficacy in neuroblastoma, CNS tumors, and sarcomas, focusing on safety and progression-free ...

5. targetedonc.com targetedonc.com/view/amxt-1501-and-dfmo-combination-achieve-fda-orphan-drug-designation

AMXT 1501 and DFMO Combination Achieve FDA Orphan ... FDA designates AMXT 1501 and DFMO as an orphan drug for neuroblastoma, aiming to enhance treatment outcomes for pediatric patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10637404/

Glioma Metabolic Feedback In Situ: A First-In-Human ... SAFETY CONSIDERATIONS. A Phase I study evaluating the safety and tolerability of DFMO and AMXT-1501 is nearing completion for patients with solid tumors ...