DFMO for Medulloblastoma

Recruiting at 16 trial locations

Overseen By BCC Enroll

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Giselle Sholler

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Metastatic outside CNS, Uncontrolled infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called Difluoromethylornithine (DFMO) for individuals with medulloblastoma, a type of brain cancer. The goal is to determine if DFMO can serve as a maintenance therapy for high-risk or relapsed cases. Participants must have a confirmed diagnosis of medulloblastoma and show stable or no evidence of disease after previous treatments. This trial may suit those who have recently undergone brain cancer treatments and meet specific medical criteria. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other anticancer medications before participating. If you are on an investigational drug or other anticancer agents, you will need to stop those before joining the study.

Is there any evidence suggesting that Difluoromethylornithine (DFMO) is likely to be safe for humans?

Research has shown that the drug DFMO is being tested for its safety and tolerability in treating medulloblastoma, a type of brain cancer. Studies with DFMO have identified common side effects, including hearing loss, ear infections, and fever. Specifically, a study with 360 patients reported these as the most frequent issues.

Despite these side effects, DFMO is generally well-tolerated. It is already used to treat other conditions, such as high-risk neuroblastoma, indicating a degree of safety for humans. However, prospective trial participants should consult their doctor about potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Difluoromethylornithine (DFMO) is unique because it targets a different pathway in medulloblastoma treatment. While traditional treatments like surgery, radiation, and chemotherapy aim to remove or kill cancer cells directly, DFMO works by inhibiting the polyamine synthesis pathway, which is essential for cancer cell growth and proliferation. Researchers are excited about DFMO because it offers a novel mechanism of action that could potentially reduce tumor growth and improve outcomes without the harsh side effects associated with conventional therapies.

What evidence suggests that DFMO might be an effective treatment for medulloblastoma?

Research has shown that Difluoromethylornithine (DFMO) could be a promising treatment for high-risk medulloblastoma, a type of brain cancer. Patients with high-risk medulloblastoma often face poor outcomes, with survival rates below 50%. In this trial, participants will receive DFMO to help prevent cancer recurrence. Previous research found DFMO effective in treating other aggressive childhood cancers, such as neuroblastoma. DFMO blocks a key enzyme that cancer cells need to grow, which helps slow or stop the cancer. These findings suggest that DFMO could improve outcomes for medulloblastoma patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael A Huang, MD

Principal Investigator

Beat Childhood Cancer at Atrium Health

Are You a Good Fit for This Trial?

This trial is for young patients (0-21 years at diagnosis) with medulloblastoma, a type of brain cancer. They must have specific molecular risk factors identified and be in stable condition post-treatment. Participants need to have good organ function, acceptable blood counts, and agree to use birth control if applicable. Those who are pregnant or breastfeeding cannot join.

Inclusion Criteria

My cancer is either not detectable or is stable and not large.

Patients must have adequate organ functions at the time of registration: Hematological: Hematological recovery as defined by ANC ≥750/μL, platelets ≥30 (non-transfused x 7 days), Liver: Adequate liver function as defined by AST and ALT <10x upper limit of normal, Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or a serum creatinine based on age/gender, Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.

My cancer is a specific type without certain genetic changes.

Exclusion Criteria

Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.

I am 5 or older and my cancer has returned or didn't respond to treatment, and I haven't had radiation.

My infection is under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID for 730 days

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Long-term follow-up

Participants are monitored for overall survival

7 years

What Are the Treatments Tested in This Trial?

Interventions

• Difluoromethylornithine

Trial Overview

The study tests Difluoromethylornithine (DFMO) as a maintenance therapy for high-risk or relapsed medulloblastoma in children and young adults. It's an open-label trial, meaning both doctors and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Difluoromethylornithine (DFMO) Experimental Treatment 1 Intervention

study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.

Who Is Running the Clinical Trial?

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

Giselle SaulnierSholler

Lead Sponsor

Trials

22

Recruited

2,400+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Difluoromethylornithine (DFMO) works as an irreversible inhibitor of the enzyme ornithine decarboxylase, which is crucial for polyamine synthesis, thereby affecting cell survival and showing potential as an anticancer agent.

DFMO has demonstrated cytostatic activity and effectiveness both as a standalone treatment and in combination with other chemotherapy drugs for certain cancers and leukemias, highlighting its role in cancer treatment and prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Difluoromethylornithine in cancer: new advances. Alexiou, GA., Lianos, GD., Ragos, V., et al.[2022]

alpha-Difluoromethylornithine (DFMO) alone has minimal impact on murine glioma and rat gliosarcoma tumors, but when used before BCNU treatment, it significantly enhances the effectiveness of BCNU without increasing toxicity.

DFMO may also help slow down tumor regrowth after BCNU therapy, suggesting it could be a valuable adjunct treatment in glioma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor. Marton, LJ., Levin, VA., Hervatin, SJ., et al.[2013]

In a study involving 38 patients with various cancers, DFMO was added to conventional chemotherapy and showed negligible gastrointestinal, hematologic, and biochemical toxicity, with the main side effect being ototoxicity in 15.8% of patients.

Despite its safety profile, DFMO did not demonstrate any significant improvement in disease progression compared to conventional chemotherapy alone, indicating that it may not enhance the efficacy of standard cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II clinical trial with alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. Horn, Y., Schechter, PJ., Marton, LJ.[2019]

In a Phase I trial involving 20 patients with refractory leukemia, intravenous DFMO was found to have manageable toxicity, with nausea and vomiting being the most common side effects, and less frequent ototoxicity compared to the oral form.

While no patients achieved remission, some experienced stabilization or a decrease in circulating blast cells, indicating potential for growth inhibition, although this effect did not correlate with the dosage administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor. Maddox, AM., Keating, MJ., McCredie, KE., et al.[2019]

In phase II trials, alpha-Difluoromethylornithine (DFMO) showed antitumor activity in patients with advanced small cell lung cancer and metastatic colon cancer, indicating its potential as a treatment option.

While DFMO was generally well-tolerated, it caused thrombocytopenia in previously treated small cell lung cancer patients on a continuous dosing schedule, and both intermittent and continuous schedules led to reversible hearing loss and gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trials of alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Abeloff, MD., Rosen, ST., Luk, GD., et al.[2013]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04696029

DFMO as Maintenance Therapy for Molecular High/Very ...

In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10190116/

Difluoromethylornithine (DFMO) and Neuroblastoma

DFMO represents a promising therapeutic option for high-risk neuroblastoma, a deadly childhood cancer that currently lacks effective treatments.

3.

nortonhealthcareprovider.com

nortonhealthcareprovider.com/news/dfmo-medulloblastoma-clinical-trial

DFMO medulloblastoma clinical trial examines drug's ...

Medulloblastoma patients with molecular high-risk or very high-risk features have more dismal outcomes. Survival drops to < 50% in patients with ...

4.

fda.gov

fda.gov/media/172726/download

Eflornithine (DFMO) for patients with high-risk ...

FDA can conclude that one adequate and well-controlled clinical investigation plus confirmatory evidence is sufficient to establish ...

5.

archildrens.org

archildrens.org/research/clinical-trials/eflornithine-dfmo-as-maintenance-therapy

DFMO as Maintenance Therapy for Molecular High/Very ...

This study seeks to evaluate how well the DFMO works to prevent relapse in patients with high risk and very high risk medulloblastoma.

6.

fda.gov

fda.gov/media/172661/download

eflornithine (dfmo) tablets to reduce the risk of

... DFMO benefit in patients with HRNB. The confirmatory data supporting DFMO as an effective maintenance treatment for HRNB is summarized in ...

7.

researchgate.net

researchgate.net/figure/Study-Safety-Data-Toxicity-of-Oral-DFMO-and-Etoposide_fig8_277410133

Study Safety Data: Toxicity of Oral DFMO and Etoposide.

We found that overexpression of AZIN1 in medulloblastoma cells induces phenotypically aggressive features. Conducting in vivo studies we found that knocking-out ...

8.

cclg.org.uk

cclg.org.uk/sites/default/files/2025-03/cclg-dfmo-statement-for-patients-and-families-8-10-24.pdf

Eflornithine (DFMO) in the treatment of high-risk ...

Data from. 360 patients was assessed for toxicity and safety; the most common adverse reactions were hearing loss, ear infection, fever, ...