MIBG + Chemotherapy for Neuroblastoma

Recruiting at 34 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Oncology Group

Disqualifiers: Pregnancy, Breastfeeding, Prior radiation, others

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

Compensation: Varies

Number of Visits: 8

99 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of radioisotope therapy and chemotherapy for patients with high-risk neuroblastoma, a cancer affecting nerve cells. The study examines whether iobenguane I 131 (a type of targeted radiation therapy) combined with chemotherapy drugs like carboplatin and etoposide phosphate can effectively kill cancer cells. Eligible patients are those newly diagnosed with stage 3 or 4 neuroblastoma who have received minimal prior treatment, aside from some emergency interventions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients must not have had prior systemic therapy, except for certain emergency treatments, which might imply some restrictions. It's best to discuss your current medications with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Iobenguane I-131 is generally safe and well-tolerated in patients with certain cancers, as past studies reported no major issues or side effects from this treatment.

Busulfan has been used for many years to treat high-risk neuroblastoma. Evidence suggests it improves patient outcomes when combined with other treatments, indicating relative safety. However, like many cancer treatments, it can cause side effects.

Cyclophosphamide is often included in initial treatment plans for neuroblastoma. Studies indicate it is well-tolerated, allowing patients to undergo treatment without severe side effects.

Etoposide has been part of various cancer treatments for a long time. Despite reports of side effects, it is generally considered compatible with other cancer drugs.

Melphalan, often used with busulfan, helps improve survival rates in high-risk neuroblastoma patients. Research suggests it is safe, though it may cause side effects like other chemotherapy drugs.

These treatments have been studied in different settings and are generally safe when used carefully. Discuss potential risks and benefits with a doctor to determine the best approach for your situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the MIBG plus chemotherapy treatment for neuroblastoma because it combines traditional chemotherapy drugs with a radioactive compound, Iobenguane I-131, which specifically targets cancer cells. Unlike standard treatments that mainly use chemotherapy to kill fast-growing cells, this approach uses Iobenguane I-131 to deliver targeted radiation directly to the tumor, potentially reducing damage to healthy tissues. This targeted action offers a promising new mechanism that could enhance treatment effectiveness and reduce side effects, making it an innovative option for tackling this aggressive cancer.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that iobenguane I-131, also known as 131I-MIBG, holds promise for treating high-risk neuroblastoma. In this trial, participants will receive a combination of 131I-MIBG and chemotherapy. Studies indicate that using 131I-MIBG with stem cell transplants can achieve response rates of up to 71%. The chemotherapy drugs busulfan and melphalan, part of this trial's regimen, have improved event-free survival in similar cases, raising survival rates to 49%. Cyclophosphamide and etoposide phosphate, also included in the trial, have proven effective in other neuroblastoma treatments, showing good response rates and manageable side effects. Together, these treatments target and destroy tumor cells, offering hope for better outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Brian D Weiss

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children with high-risk neuroblastoma, a type of cancer. Eligible patients are those newly diagnosed with specific stages of the disease, have certain genetic features like MYCN amplification, and meet age requirements. They should not have had much prior treatment except possibly one round of chemotherapy or emergency radiation. Kidney function tests and heart function must be within acceptable ranges.

Inclusion Criteria

Shortening fraction >= 27% by echocardiogram or

I am older than 18 months and my cancer has unfavorable pathology.

I am over 1 year old with a specific type of stage 2 neuroblastoma.

Exclusion Criteria

I haven't had high-dose radiation to my kidneys or liver.

I am breastfeeding but agree to stop if I join the trial.

Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive 5 courses of induction therapy with various chemotherapy agents and undergo peripheral blood stem cell collection.

15 weeks

5 courses, each 21 days apart

Iobenguane I 131 Induction Therapy

Participants receive iobenguane I 131 IV over 90-120 minutes on day 1, beginning 3-6 weeks after course 5 of induction chemotherapy.

1 day

Consolidation Therapy

Participants receive busulfan and melphalan chemotherapy followed by autologous stem cell rescue.

10-12 weeks

Radiotherapy

Participants undergo 12 fractions of external-beam radiotherapy to all areas of residual disease.

Approximately 2 weeks

Maintenance Therapy

Participants receive isotretinoin orally twice daily on days 1-14, repeating every 28 days for 6 courses.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

10 years

Every 3 months for 1 year, every 6 months for 4 years, then annually for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Busulfan
• Cyclophosphamide
• Etoposide Phosphate
• Iobenguane I-131
• Isotretinoin
• Melphalan

Trial Overview The study tests induction therapy including iobenguane I-131 (a radioactive drug) plus various chemotherapies followed by stem cell transplant and maintenance therapy with isotretinoin. The goal is to see if this combination can better kill tumor cells in these young patients.

How Is the Trial Designed?

Group I: Treatment (131I-MIBG, chemotherapy) Experimental Treatment 19 Interventions

See Detailed Description.

Busulfan is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Malignant lymphoma
• Bone marrow transplantation conditioning

Approved in European Union as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a pilot study involving 68 children with newly diagnosed high-risk neuroblastoma, 86.8% completed induction chemotherapy and received 131 I-MIBG therapy, demonstrating the treatment's feasibility.

The study found that while there were some severe side effects, including sinusoidal obstruction syndrome (SOS), the 15 mCi/kg dose of 131 I-MIBG showed a high feasibility rate of 96.7%, supporting further investigation in a larger randomized trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Weiss, BD., Yanik, G., Naranjo, A., et al.[2022]

Serotonin receptor antagonists and corticosteroids are the most effective anti-emetics for managing chemotherapy-induced nausea and vomiting, with minimal side effects and convenient administration options.

The guidelines recommend using these anti-emetics in combination for highly emetogenic chemotherapy and as single agents for moderately emetogenic regimens, emphasizing that appropriate use can improve patient quality of life and reduce healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for anti-emetic therapy: acute emesis. Fauser, AA., Fellhauer, M., Hoffmann, M., et al.[2019]

In a study involving 413 chemotherapy-naïve patients, NEPA, a combination of netupitant and palonosetron, was found to be safe and well-tolerated, with a low incidence of adverse events such as constipation (3.6%) and headache (1.0%).

NEPA demonstrated high efficacy in preventing chemotherapy-induced nausea and vomiting, achieving a complete response rate of 81% in the first cycle, which was maintained over multiple cycles of highly and moderately emetogenic chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Gralla, RJ., Bosnjak, SM., Hontsa, A., et al.[2023]

In a study involving 1347 patients with high-risk neuroblastoma, the high-dose chemotherapy regimen of busulfan and melphalan resulted in a significantly better 3-year event-free survival rate of 50% compared to 38% for the carboplatin, etoposide, and melphalan regimen.

The busulfan and melphalan treatment also led to fewer severe adverse events, with only 4% of patients experiencing life-threatening toxicities, compared to 10% in the carboplatin, etoposide, and melphalan group, suggesting it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Ladenstein, R., Pötschger, U., Pearson, ADJ., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26524264/

Tandem high-dose chemotherapy with thiotepa and ... We report the results of an intensified high-dose chemotherapy (HDC) strategy to improve the prognosis of VHR patients. This strategy was based on tandem HDC ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-high-risk-neuroblastoma-treatment-with-busulfan-melphalan-and-drug-combination-for-patients-with-insufficient-metastatic-response/

Study on High-Risk Neuroblastoma Treatment with ... This clinical trial evaluates the efficacy of Busulfan and Melphalan, among other drugs, in treating high-risk neuroblastoma in patients ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.10527

Report from the European HR-NBL1/Siopen trial. EFS was better with BUMEL/SCR given ≤ 240days (421pts) after diagnosis (0.41±0.02) than for 54 pts taking longer (0.16±0.05; p < 0.0001). Outcome was not ...

4. theoncologynurse.com theoncologynurse.com/articles/ton-3328

New Standard of Care with Busulfan/Melphalan Regimen ... After a median follow-up of 3.5 years, the event-free survival rate was 49% in the busulfan/melphalan group compared with 33% in the CEM group. Randomization ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725003161

Comparison of Busulfan and Treosulfan-Based High-Dose ... The 5-year OS (overall survival) and EFS (event-free survival) rates for the entire cohort were 85.3% and 67.1%, respectively. In the busulfan group (n=20), the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27042850/

Busulfan-melphalan in high-risk neuroblastoma We report the results of the 30-year experience of a cohort of patients with HR-NBL treated with high-dose (HD) busulfan (Bu)-containing regimens.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721007491

Myeloablative Busulfan/Melphalan Consolidation following ... INTRODUCTION. Over the past decade, outcomes for patients with high-risk neuroblastoma have improved significantly, with 3-year event-free survival (EFS) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01798004

Busulfan, Melphalan, and Stem Cell Transplant After ... This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8855886/

Myeloablative Busulfan/Melphalan (BuMel) Consolidation ... Over the past decade, outcomes for patients with high-risk neuroblastoma have improved significantly, with 3-year event-free survival (EFS) approximately 50 ...

10. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30070-0/abstract

Busulfan and melphalan versus carboplatin, etoposide, ... Busulfan and melphalan improved event-free survival in children with high-risk ... Long-term results for children with high-risk neuroblastoma ...