Radioactive MIBG for Neuroblastoma

Overseen By Shakeel Modak, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Severe organ toxicity, Infections, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to find how active and safe 131 I-MIBG is in patients with resistant neuroblastoma, malignant pheochromocytoma and malignant paraganglioma.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does require a waiting period after certain treatments: at least 2 weeks after any biologic therapy and 3 weeks after the last dose of chemotherapy.

What data supports the effectiveness of the drug Iobenguane I 131 for treating neuroblastoma?

Research shows that Iobenguane I 131 is an effective treatment for neuroblastoma, with response rates over 30% in cases where the disease is resistant to other treatments. However, the exact role of this drug in managing neuroblastoma is still unclear, and more studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

What safety data exists for Radioactive MIBG treatment in humans?

Radioactive MIBG treatment for neuroblastoma has shown some side effects, mainly affecting the blood (myelosuppression) and thyroid. There is also a risk of developing second cancers and primary hypothyroidism (underactive thyroid) after treatment. ^{1 5 6 7 8}

What makes the drug Iobenguane I 131 unique for treating neuroblastoma?

Iobenguane I 131 is unique because it is a targeted radiopharmaceutical that specifically seeks out neuroblastoma cells, delivering radiation directly to the tumor, which can be effective even in advanced or treatment-resistant cases. Unlike conventional treatments, it can be used at diagnosis or in relapsed cases, and it has shown promising results with manageable side effects, primarily affecting blood cell production. ^{2 5 9 10 11}

Research Team

Ellen Basu, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients with recurrent or resistant neuroblastoma, malignant pheochromocytoma, or paraganglioma. Participants must be over 1 year old, have a life expectancy of at least eight weeks, and be able to follow radiation safety procedures. They need stored stem cells for re-infusion post-treatment. Pregnant women and those unable to comply with safety protocols are excluded.

Inclusion Criteria

My neuroblastoma diagnosis is confirmed by specific tests and criteria.

My cancer has grown, come back, or didn't fully respond to standard treatments.

Signed informed consent indicating awareness of the investigational nature of this program

Exclusion Criteria

I am not pregnant and will use birth control during the study.

My major organs are mostly healthy, except I may have a serious hearing problem.

I have a serious infection that antibiotics can't control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive targeted radiotherapy with I-131 MIBG to assess activity and safety in resistant neuroblastoma or malignant chromaffin cell tumors

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Iobenguane I 131

Trial Overview The study tests the activity and safety of Iodine I 131 Metaiodobenzylguanidine (131 I-MIBG) in treating certain cancers that haven't responded well to other treatments. It aims to understand how effective this treatment is against these specific conditions.

Participant Groups

Group I: Radiation Experimental Treatment 1 Intervention

Iobenguane I 131 is already approved in United States for the following indications:

Approved in United States as Azedra for:

• Pheochromocytoma
• Paraganglioma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 21 patients with refractory neuroblastoma, the maximum-tolerated dose of iodine-131-metaiodobenzylguanidine ((131)I-MIBG) was established at 36 mCi/kg, with no dose-limiting toxicities observed, allowing for safe dose intensification.

The treatment showed promising efficacy, with a response rate including two partial responses and eight mixed responses, indicating that (131)I-MIBG can be a viable option for patients despite the challenges of radiation safety and hematologic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. Matthay, KK., Quach, A., Huberty, J., et al.[2021]

In a study of 218 patients with neuroblastoma treated with (131)I-MIBG, the overall response rate to the treatment was 27%, with no significant difference between patients with relapsed and refractory disease.

However, relapsed patients experienced higher rates of disease progression and lower overall survival at 24 months (38.7%) compared to refractory patients (65.3%), indicating that prior relapse negatively impacts treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different outcomes for relapsed versus refractory neuroblastoma after therapy with (131)I-metaiodobenzylguanidine ((131)I-MIBG). Zhou, MJ., Doral, MY., DuBois, SG., et al.[2022]

(131)I-meta iodobenzylguanidine ((131)I-mIBG) is an active treatment for neuroblastoma, showing a variable objective tumor response rate of 0% to 75% across 25 studies, with a mean response of 32%.

Despite its activity, the optimal use and effectiveness of (131)I-mIBG remain unclear due to the lack of randomized controlled trials and significant heterogeneity in study designs, highlighting the need for more rigorous prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. Wilson, JS., Gains, JE., Moroz, V., et al.[2022]

The study successfully produced [124I]mIBG with a high radioiodide incorporation yield of 62-70%, demonstrating an effective method for radiolabelling that could enhance diagnostic imaging.

The average specific radioactivity of the formulated [124I]mIBG was 4.1 TBq μmol-1, indicating a potent tracer for PET/CT imaging in detecting metastatic neuroblastoma, which could improve diagnostic accuracy in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis of no-carrier-added meta-[124I]iodobenzylguanidine for PET imaging of metastatic neuroblastoma. Green, M., Lowe, J., Kadirvel, M., et al.[2020]

In a study involving 28 heavily pre-treated patients with neuroblastoma, multiple infusions of (131)I-MIBG resulted in a 39% overall disease response rate, indicating its efficacy as a targeted radiotherapy for refractory cases.

The main side effect observed was myelosuppression, with a significant number of patients requiring platelet transfusions, highlighting the need for careful monitoring and potential stem cell support during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for refractory neuroblastoma. Howard, JP., Maris, JM., Kersun, LS., et al.[2013]

In a study of 14 long-term survivors of neuroblastoma treated with 131-I-MIBG, 12 patients developed primary hypothyroidism, indicating that thyroid dysfunction is a common side effect of this treatment.

The degree of thyroid failure did not significantly correlate with the cumulative dose of 131-I-MIBG, suggesting that thyroid protection strategies beyond iodide supplementation may be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma. Picco, P., Garaventa, A., Claudiani, F., et al.[2019]

In a review of 119 neuroblastoma cases treated with (131)I-MIBG, five patients developed second malignant neoplasms, including two cases of myeloid leukemia, highlighting a potential risk associated with this treatment.

The findings suggest that while (131)I-MIBG is effective for targeting neuroblastoma, the occurrence of second cancers necessitates careful monitoring and consideration in treatment plans, advocating for an international registry to track these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine. Garaventa, A., Gambini, C., Villavecchia, G., et al.[2013]

In a study of 213 high-risk neuroblastoma patients treated with (131) I-MIBG, the amount of radiation exposure (whole-body radiation dose, WBD) correlated with the administered activity of (131) I-MIBG per kilogram, indicating that dosage can predict radiation exposure levels.

However, the study found no significant relationship between WBD and treatment response or toxicity, suggesting that factors other than whole-body radiation exposure may influence patient outcomes, and highlighting the need for future research on tumor-specific dosimetry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Whole-Body Radiation Dose on Response and Toxicity in Patients With Neuroblastoma After Therapy With 131 I-Metaiodobenzylguanidine (MIBG). Trieu, M., DuBois, SG., Pon, E., et al.[2020]

High doses of 131I-MIBG have shown effectiveness in treating resistant neuroblastoma, even in advanced cases, with patients achieving significant tumor reduction and no major side effects.

In two children with stage III neuroblastoma, low doses of 131I-MIBG led to a notable decrease in tumor mass, suggesting that even small doses can effectively target and destroy tumor cells that uptake the drug, while preserving the option for future chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[131I]metaiodobenzylguanidine in neuroblastoma patients at diagnosis. Mastrangelo, R., Lasorella, A., Troncone, L., et al.[2016]

The study established that a maximum tolerated dose of no-carrier-added (NCA) (131)I-MIBG at 666 MBq/kg can be administered safely to children with resistant neuroblastoma, without significant nonhematologic toxicity.

Out of 15 patients treated, 4 showed a complete or partial response to the therapy, indicating promising efficacy in targeting neuroblastoma tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. Matthay, KK., Weiss, B., Villablanca, JG., et al.[2022]

No-carrier-added [131I]MIBG shows enhanced uptake in neuroblastoma cells compared to conventional [131I]MIBG, indicating a potentially improved therapeutic ratio for targeted radiotherapy.

The study found that no-carrier-added [131I]MIBG significantly inhibited tumor regrowth and accumulated more in tumor tissues than the conventional preparation, suggesting clinical advantages for its use in treating neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation. Mairs, RJ., Cunningham, SH., Russell, J., et al.[2013]

References

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

Iodine-131--metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Different outcomes for relapsed versus refractory neuroblastoma after therapy with (131)I-metaiodobenzylguanidine ((131)I-MIBG). [2022]

3. England pubmed.ncbi.nlm.nih.gov

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Radiosynthesis of no-carrier-added meta-[124I]iodobenzylguanidine for PET imaging of metastatic neuroblastoma. [2020]

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

Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for refractory neuroblastoma. [2013]

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

Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma. [2019]

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

Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine. [2013]

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

Impact of Whole-Body Radiation Dose on Response and Toxicity in Patients With Neuroblastoma After Therapy With 131 I-Metaiodobenzylguanidine (MIBG). [2020]

9. Italy pubmed.ncbi.nlm.nih.gov

[131I]metaiodobenzylguanidine in neuroblastoma patients at diagnosis. [2016]

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

Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. [2022]

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

No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation. [2013]