MIBG + Chemotherapy for Neuroblastoma

Recruiting at 33 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

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies induction therapy followed by iobenguane I 131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as iobenguane I 131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide phosphate, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that are destroyed by iobenguane I 131 and chemotherapy. Giving radioisotope therapy, chemotherapy, and peripheral stem cell transplant may kill more tumor cells.

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.

What data supports the effectiveness of the drug combination MIBG + Chemotherapy for Neuroblastoma?

Research shows that high-dose chemotherapy with busulfan and melphalan, combined with stem cell rescue, improves survival in high-risk neuroblastoma patients. Additionally, the combination of I-MIBG therapy with busulfan/melphalan has been shown to be feasible and safe, with some patients achieving complete remission or stable disease. ^{1 2 3 4 5}

Is the combination of MIBG and chemotherapy safe for humans?

The research articles provided do not contain specific safety data for the combination of MIBG and chemotherapy drugs like Busulfan, Cyclophosphamide, Etoposide, Iobenguane I-131, Isotretinoin, or Melphalan. They focus on antiemetic treatments to manage nausea and vomiting during chemotherapy, which are generally well-tolerated and have low toxicity. ^{6 7 8 9 10}

How does the MIBG + Chemotherapy treatment for neuroblastoma differ from other treatments?

This treatment combines a radioactive drug, Iobenguane I-131, which targets neuroblastoma cells, with high-dose chemotherapy drugs like busulfan and melphalan, followed by a stem cell transplant. This approach is unique because it uses targeted radiation to improve remission before intense chemotherapy, which is not typical in standard treatments for neuroblastoma. ^{3 11 12 13 14}

Research Team

Brian D Weiss

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

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

Long-term results of the combination of the N7 induction chemotherapy and the busulfan-melphalan high dose chemotherapy. [2014]

2. England 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. [2022]

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

Feasibility of Busulfan Melphalan and Stem Cell Rescue After 131I-MIBG and Topotecan Therapy for Refractory or Relapsed Metastatic Neuroblastoma: The French Experience. [2019]

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

A Phase I New Approaches to Neuroblastoma Therapy Study of Buthionine Sulfoximine and Melphalan With Autologous Stem Cells for Recurrent/Refractory High-Risk Neuroblastoma. [2022]

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

Immunochemotherapy in advanced neuroblastoma. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study. [2019]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The 5HT3-receptor antagonist Zofran (ondansetron) as an agent for preventing nausea and vomiting during the cytostatic treatment of cancer patients]. [2013]

8. England 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. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Guidelines for anti-emetic therapy: acute emesis. [2019]

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

131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma. [2018]

13. United States 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. [2022]

14. Germany pubmed.ncbi.nlm.nih.gov

[131(I)-meta-iodobenzylguanidine treatment of 32 children with therapy-refractory neuroblastoma]. [2013]