What side effects are associated with this type of intervention?

Common treatments for neuroblastoma, such as DFMO combined with celecoxib, cyclophosphamide, and topotecan, can have several side effects. DFMO may cause gastrointestinal disturbances, hearing loss, and cytopenias. Celecoxib, a COX-2 inhibitor, can lead to gastrointestinal issues, cardiovascular risks, and renal impairment. Cyclophosphamide is known for causing myelosuppression, hemorrhagic cystitis, and secondary malignancies. Topotecan, a topoisomerase inhibitor, often results in myelosuppression, gastrointestinal symptoms, and fatigue. These side effects necessitate careful monitoring and supportive care during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for neuroblastoma, including chemotherapeutic agents and targeted therapies. While the provided context does not specify FDA-approved treatments that directly inhibit ornithine decarboxylase like DFMO, it does mention the use of DFMO in combination with other drugs in clinical trials. DFMO works by reducing polyamine synthesis, which is a novel approach in the treatment of neuroblastoma. Other FDA-approved treatments for neuroblastoma include chemotherapeutic agents like cyclophosphamide and topotecan, which are also part of the combination being studied with DFMO.

What other types of research exist?

Promising novel alternatives to DFMO for Neuroblastoma patients include: 1) GD2-targeted immunotherapies such as dinutuximab, which has shown efficacy in recurrent osteosarcoma and may be applicable to Neuroblastoma. 2) Combination therapies involving cyclophosphamide and topotecan, which are being studied in conjunction with other agents like celecoxib. 3) Newer agents like N1-dansyl-spermine, a polyamine antagonist, which has shown neuroprotective effects and could be explored for its potential in Neuroblastoma treatment.

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Nonsteroidal Anti-inflammatory Drug (NSAID)

DFMO + Celecoxib + Cyclophosphamide + Topotecan for Neuroblastoma (DFMO Trial)

Phase 1

Waitlist Available

Research Sponsored by New Approaches to Neuroblastoma Therapy Consortium

Eligibility Criteria Checklist

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

Must have

All patients must have at least ONE site of evaluable disease

Patients must have adequate heart, kidney, liver and bone marrow function

Must not have

Patients status post allogeneic stem cell transplant

Females of childbearing potential that do not have a negative pregnancy test

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 1 year

Awards & highlights

All Individual Drugs Already Approved

Approved for 20 Other Conditions

No Placebo-Only Group

Summary

This trial uses a mix of two pills and two IV medicines to treat tumors. It focuses on finding the safest dose and understanding side effects. The treatment works by reducing growth signals, lowering inflammation, and killing cancer cells.

Who is the study for?

This trial is for children and young adults aged 2-29 with high-risk neuroblastoma that's recurrent, progressive, or hasn't fully responded to standard treatment. Participants need evaluable disease but good heart, kidney, liver, and bone marrow function. They can't join if they have severe allergies to NSAIDs/aspirin/sulfonamides, are pregnant/breastfeeding without contraception use, have major organ issues or active infections.

What is being tested?

The study tests different doses of DFMO (oral) combined with celecoxib (oral), cyclophosphamide (IV), and topotecan (IV) in patients with neuroblastoma. It aims to find the highest tolerable dose of DFMO without severe side effects and assess its impact on tumor size and specific gene changes related to treatment response.

What are the potential side effects?

Potential side effects include those common to chemotherapy like nausea, hair loss, low blood cell counts leading to increased infection risk; plus possible stomach irritation from celecoxib. The severity may vary based on the DFMO dosage.

Eligibility Criteria

Inclusion Criteria

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

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I have at least one tumor that can be measured for treatment response.

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My heart, kidneys, liver, and bone marrow are functioning well.

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I am between 2 and 30 years old.

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My neuroblastoma is high-risk and has not fully responded to standard treatments.

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My bone marrow works well enough for me to join the study.

Exclusion Criteria

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

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I have had a stem cell transplant from a donor.

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I am a woman who can have children and I do not have a negative pregnancy test.

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I have not had a seizure or been on seizure medication in the last year.

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I do not have any active or uncontrolled infections.

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I have active stomach bleeding or symptoms like gastritis.

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My major organs are healthy enough to handle treatment.

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I am currently receiving hemodialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 1 year

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

Treatment Details

Study Objectives

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

Primary study objectives

Number of participants with adverse events as a measure of safety and tolerability.

Side effects data

From 2024 Phase 1 & 2 trial • 16 Patients • NCT02139397

33%

Anemia

33%

Neutropenia

33%

Alanine aminotransferase increased

33%

Anorexia

33%

Peripheral sensory neuropathy

100%

80%

60%

40%

20%

Study treatment Arm

Phase I: DFMO 1500 mg/m^2

Phase I: DFMO 2000 mg/m^2

Phase I: DFMO 2500 mg/m^2

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

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: DFMO, Celecoxib, Cyclophosphamide & TopotecanExperimental Treatment4 Interventions

Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). \*Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DFMO

2014

Completed Phase 2

~240

Celecoxib

FDA approved

Cyclophosphamide

FDA approved

Topotecan

FDA approved

0 / 12Eligibility 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

Neuroblastoma treatments often target the rapid cell growth characteristic of this cancer. DFMO (difluoromethylornithine) inhibits ornithine decarboxylase, reducing polyamine synthesis, which is crucial for cell proliferation. This mechanism is significant as it directly impedes the growth of cancer cells. Additionally, chemotherapy agents like cyclophosphamide and topotecan work by damaging DNA and inhibiting topoisomerase I, respectively, leading to cell death. Targeted therapies, such as those inhibiting specific genetic mutations, also play a role. These treatments are vital for Neuroblastoma patients as they offer multiple avenues to halt tumor growth and improve survival rates.

Parkinsonism. Clinical and neuropharmacologic aspects.Dopamine: an old target in a new therapy.Presynaptic regulation of extracellular dopamine levels in the medial prefrontal cortex and striatum during tyrosine depletion.