What side effects are associated with this type of intervention?

Common treatments for neuroblastoma, including chemotherapy, radiation therapy, and immunotherapy, have various side effects. Chemotherapy can cause nausea, vomiting, hair loss, and increased infection risk. Radiation therapy may lead to skin irritation, fatigue, and long-term growth effects. Immunotherapy can result in fever, chills, fatigue, and allergic reactions. DFMO, which inhibits polyamine synthesis, may cause gastrointestinal disturbances, hearing loss, and cytopenias. These side effects are generally manageable with careful monitoring.

What prior FDA approvals exist?

The FDA has approved several treatments for neuroblastoma, primarily focusing on high-risk cases. These include chemotherapeutic agents like cyclophosphamide, doxorubicin, and vincristine, as well as targeted therapies such as dinutuximab, an anti-GD2 monoclonal antibody. While specific FDA approvals for drugs that inhibit ornithine decarboxylase like DFMO are not detailed, DFMO itself is being studied for its potential to prevent recurrence in high-risk neuroblastoma patients by reducing polyamine synthesis necessary for cell proliferation.

What other types of research exist?

Promising novel alternatives to DFMO for neuroblastoma treatment include: 1) Anti-GD2 antibodies such as dinutuximab, which target disialoganglioside GD2 on neuroblastoma cells. 2) ALK inhibitors like crizotinib for patients with ALK mutations. 3) Immune checkpoint inhibitors such as pembrolizumab, which enhance the immune response against tumor cells. 4) CAR T-cell therapies targeting GD2 or other neuroblastoma-specific antigens. These therapies have shown potential in clinical trials and may offer new avenues for treatment in 2024.

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DFMO Maintenance Therapy for Neuroblastoma (NMTT Trial)

Q: What is the mechanism of action of this treatment?

Difluoromethylornithine (DFMO) treats Neuroblastoma by inhibiting ornithine decarboxylase, reducing polyamine synthesis necessary for cell proliferation, thereby limiting cancer cell growth. This targeted approach is crucial for Neuroblastoma patients as it may lead to fewer side effects and better outcomes. Other treatments like chemotherapy and immunotherapy also play vital roles by targeting rapidly dividing cells and enhancing the immune response, respectively, offering multiple strategies to improve remission and survival rates.

Phase 2

Recruiting

Research Sponsored by Giselle Sholler

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have adequate organ functions at the time of registration: Hematological: Total absolute phagocyte count ≥1000/μL, Liver: Subjects must have adequate liver function, Renal: Adequate renal function, 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.

Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.

Must not have

BSA (Body Surface Area) of <0.25 m2.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a medication called DFMO in patients with high-risk neuroblastoma who are in remission. The goal is to prevent the cancer from returning by stopping an enzyme that cancer cells need to grow. DFMO was initially developed as a cancer therapeutic agent but gained renewed interest as a preventive agent after showing effectiveness in inhibiting cancer development in rodent models.

Who is the study for?

This trial is for high-risk neuroblastoma patients under 30.99 years old in remission after intensive treatment, including chemotherapy, surgery, stem cell transplant, radiotherapy, immunotherapy with dinutuximab and retinoic acid. They must have no residual disease or bone marrow involvement over 10%, be within a specific time frame post-treatment, agree to birth control if applicable, and not be on other investigational drugs.

What is being tested?

The trial tests DFMO as an oral maintenance therapy for preventing neuroblastoma recurrence. Participants will take DFMO daily for two years at doses adjusted by body surface area. The study includes multiple patient groups based on their previous response to standard therapies.

What are the potential side effects?

While the description doesn't specify side effects of DFMO directly, potential side effects may include hearing loss and mild blood disorders since it's being tested as a cancer drug; however individual experiences can vary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can do most activities and am expected to live for at least 2 more months.

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My scans show no signs of cancer, and my bone marrow is clear.

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I have had cancer come back but am now in remission again.

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My neuroblastoma responded well to treatment before a transplant, with less than 10% cancer in my bone marrow.

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My neuroblastoma is in its first complete remission after initial standard treatment.

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I've completed the specific treatment steps for my cancer as outlined, including chemotherapy, surgery, stem cell transplant, radiotherapy, and immunotherapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My body surface area is less than 0.25 square meters.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Area under the plasma concentration versus time curve (AUC)

Peak Plasma Concentration (Cmax)

Time to reach Peak Plasma Concentration (Tmax)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Difluoromethylornithine (DFMO)Experimental Treatment1 Intervention

Subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Difluoromethylornithine (DFMO) treats Neuroblastoma by inhibiting ornithine decarboxylase, reducing polyamine synthesis necessary for cell proliferation, thereby limiting cancer cell growth. This targeted approach is crucial for Neuroblastoma patients as it may lead to fewer side effects and better outcomes. Other treatments like chemotherapy and immunotherapy also play vital roles by targeting rapidly dividing cells and enhancing the immune response, respectively, offering multiple strategies to improve remission and survival rates.