What side effects are associated with this type of intervention?

The most common treatments for neuroblastoma, such as Difluoromethylornithine (DFMO) and Etoposide, have several known side effects. DFMO can cause gastrointestinal disturbances, hearing loss, and cytopenias. Etoposide is associated with side effects including myelosuppression (leading to increased risk of infection and bleeding), gastrointestinal symptoms (nausea, vomiting, diarrhea), alopecia, and potential secondary malignancies. Both treatments require careful monitoring to manage these adverse effects effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of neuroblastoma, often used in combination therapies. Etoposide, a DNA topoisomerase II inhibitor, is commonly used in various chemotherapy regimens for neuroblastoma. While Difluoromethylornithine (DFMO) is still under investigation, other drugs like cyclophosphamide, doxorubicin, and vincristine have been approved and are frequently used in treatment protocols. These drugs work through different mechanisms, including DNA cross-linking and inhibition of topoisomerase II, similar to Etoposide.

What other types of research exist?

Promising novel alternatives for Neuroblastoma treatment include: 1) Anti-GD2 antibody therapies 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 specific antigens on neuroblastoma cells. These alternatives have shown potential in clinical trials and may offer new hope for patients in 2024.

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Anti-cancer drug

DFMO + Etoposide for Neuroblastoma

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

Difluoromethylornithine (DFMO) inhibits ornithine decarboxylase, reducing polyamine synthesis essential for cell proliferation, thereby inhibiting tumor growth. Etoposide inhibits DNA topoisomerase II, causing DNA breaks and cell death. These mechanisms are crucial for Neuroblastoma patients as they target the rapid cell division and growth of cancer cells, helping to halt tumor progression.

Phase 2

Recruiting

Research Sponsored by Giselle SaulnierSholler

Eligibility Criteria Checklist

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

Must have

i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).

ii. No evidence of disease metastatic to bone marrow.

Must not have

Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.

BSA of <0.25 m2.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years plus 5 years follow up

Awards & highlights

Summary

This trial uses two drugs, DFMO and etoposide, to treat children whose neuroblastoma has come back or didn't respond to initial treatments. DFMO stops cancer cells from growing, and etoposide helps kill them. The study includes patients who are recovering after additional therapy, those who have had the disease return but are currently without symptoms, and those with active disease. DFMO has been evaluated as a follow-up treatment for severe neuroblastoma in previous studies.

Who is the study for?

This trial is for individuals under 31 years old with neuroblastoma that has come back or didn't respond to treatment. They must have completed at least 4 cycles of intense chemotherapy, have good organ function, and a performance score of 60% or higher. Women who can have children need a negative pregnancy test and agree to use birth control.

What is being tested?

The study tests Eflornithine (DFMO) in combination with etoposide on patients with relapsed/refractory neuroblastoma. It's an open-label, multicenter trial meaning all participants know what treatment they're getting and it involves multiple locations.

What are the potential side effects?

Possible side effects include suppression of bone marrow leading to low blood counts, digestive issues from etoposide such as nausea or vomiting, potential liver problems indicated by changes in certain blood tests, fatigue, hair loss, and allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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My scans show no remaining cancer.

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My cancer has not spread to my bone marrow.

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I have completed at least 4 cycles of intense chemotherapy.

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I do not have active symptoms from a transplant rejection.

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It has been over 8 weeks since my last MIBG therapy.

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It has been over 2 months since my transplant.

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I can do most activities but may need help.

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My cancer can be seen on scans or confirmed through a biopsy.

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I am 30 years old or younger with a confirmed neuroblastoma diagnosis that has come back or didn't respond to treatment.

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My liver functions are within the required range.

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My kidney function is good based on tests.

Exclusion Criteria

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

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I have never taken DFMO at a dose higher than 1000mg/m2 twice a day before this study.

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My body surface area is less than 0.25 square meters.

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I am not currently on any cancer treatments and have recovered from previous ones.

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I have never taken DFMO with etoposide.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years plus 5 years follow up

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years plus 5 years follow up

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years plus 5 years follow up 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 event free survival (EFS) during study

Secondary study objectives

Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria.

Length of time that participants experience Overall Survival (OS)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Side effects data

From 2019 Phase 3 trial • 171 Patients • NCT01483144

21%

nausea

14%

abdominal pain

14%

upper respiratory tract infection

14%

headache

13%

abdominal pain upper

13%

gastroenteritis

13%

diarrhoea

13%

rectal haemorrhage

11%

haematochezia

11%

nasopharyngitis

11%

rash

11%

vomiting

flatulence

influenza like illness

back pain

oropharyngeal pain

fatigue

myalgia

arthralgia

dizziness

influenza

sinusitis

constipation

gastritis erosive

pouchitis

small bowel obstruction

gastroenteritis viral

neck pain

cough

pruritus

dry skin

urticaria

small intestinal obstruction

abdominal distension

weight increased

decreased appetite

dyspepsia

anxiety

alopecia

urinary tract infection

seroma

ileus

inguinal hernia

pancreatitis acute

wound dehiscence

bursitis

pulmonary mass

seasonal allergy

contusion

insomnia

nasal congestion

hyperglycaemia

bronchitis

nephritis

renal failure acute

depression

lung adenocarcinoma

ear pain

psychotic disorder

100%

80%

60%

40%

20%

Study treatment Arm

Eflornithine Plus Sulindac

Eflornithine Plus Sulindac Placebo

Sulindac Plus Eflornithine Placebo

Trial Design

1Treatment groups

Experimental Treatment

Group I: Eflornithine (DFMO)Experimental Treatment1 Intervention

In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone. Etoposide will be given at 50 mg/m2/dose PO daily for the first 14 days of each 21 days until 6 cycles of etoposide are completed. DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Eflornithine

1998

Completed Phase 3

~830

0 / 15Eligibility 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) inhibits ornithine decarboxylase, reducing polyamine synthesis essential for cell proliferation, thereby inhibiting tumor growth. Etoposide inhibits DNA topoisomerase II, causing DNA breaks and cell death. These mechanisms are crucial for Neuroblastoma patients as they target the rapid cell division and growth of cancer cells, helping to halt tumor progression.

[A case of sacral neuroblastoma in an adult successfully treated with combination chemotherapy].