DFMO for Medulloblastoma

Recruiting at 15 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

Trial Summary

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 DFMO generally safe for humans?

DFMO has been tested in humans for various cancers, and while it can cause side effects like nausea, vomiting, and reversible hearing loss, these effects are generally not severe. Hearing loss was more common with continuous use, but it improved after stopping the drug. Other side effects like gastrointestinal issues were minor. ^{1 2 3 4 5}

What is the purpose of this trial?

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma.

Research Team

Michael A Huang, MD

Principal Investigator

Beat Childhood Cancer at Atrium Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor. [2019]

2. United States 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. [2013]

3. United States 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. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Phase I-II clinical trial with alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Difluoromethylornithine in cancer: new advances. [2022]