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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Iobenguane I 131, a radioactive therapy, to assess its safety and effectiveness for individuals with difficult-to-treat neuroblastoma, pheochromocytoma, or paraganglioma. These cancers have resisted standard treatments. The trial seeks participants with these conditions whose tumors appear on an MIBG scan. It may suit those who have experienced tumor growth or recurrence after initial treatments. Participants must have certain stem cells ready for use after receiving the treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that 131 I-MIBG is likely to be safe for humans?

Research has shown that Iobenguane I 131 is generally safe. Patients with cancers detected on iobenguane scans found the treatment manageable. The most common side effects included stomach issues such as nausea and vomiting. These side effects were typically manageable and did not cause serious problems for most patients. Overall, these findings suggest that Iobenguane I 131 is safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuroblastoma?

Unlike the standard treatments for neuroblastoma, which often involve chemotherapy, surgery, or radiation, Iobenguane I 131 is unique because it uses a targeted approach. This treatment harnesses the power of a radioactive compound, MIBG, which is specifically taken up by neuroblastoma cells. Once inside, it delivers a high dose of radiation directly to the cancer cells, potentially minimizing damage to surrounding healthy tissue. Researchers are excited about Iobenguane I 131 because it offers a more focused attack on the cancer, which might lead to better outcomes for patients with fewer side effects.

What evidence suggests that Iobenguane I 131 might be an effective treatment for neuroblastoma?

Studies have shown that Iobenguane I 131, administered to participants in this trial, is promising for treating resistant neuroblastoma. It helps manage symptoms such as high blood pressure and can shrink tumors or halt their growth. Research indicates that this treatment is generally safe and well-tolerated. In trials, some patients with high-risk neuroblastoma responded positively, experiencing improvements in their condition. While not a guaranteed cure, these findings offer hope for those battling this challenging disease. ^{1 3 6 7 8}

Who Is on the Research Team?

Ellen Basu, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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 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]

(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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03561259

NCT03561259 | A Study of Therapeutic Iobenguane (131-I) ... The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination with Vorinostat in patients with Recurrent or Progressive ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00992173?tab=table

Efficacy and Safety of Ultratrace™ Iobenguane I 131 in ... This is a multi-center, single arm trial of two doses of 18 mCi/kg of Ultratrace iobenguane I 131 administered to subjects with high-risk neuroblastoma.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7927907/

High-specific-activity 131iodine-metaiodobenzylguanidine ... High-specific-activity 131 I-MIBG therapy improves hypertension management, induces partial radiological response or stable disease, decreases biochemical ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.4_suppl.388

Pooled safety analysis of high-specific-activity I-131 MIBG ... Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4385691/

Iodine-131 Metaiodobenzylguanidine Therapy for ... Five-year survival rates of neuroblastoma have remained approximately over 80% for infants and improved for older children from approximately 40% before 1985 to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6553226/

SUN-345 Safety Analysis of High-Specific-Activity I-131 ... Results: Gastrointestinal (GI) toxicities, especially nausea and vomiting, were the most common AEs associated with HSA I-131 MIBG. GI toxicities were not ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT240937

Pooled safety analysis of high-specific-activity I-131 MIBG ... Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between baseline ...

8. trial.medpath.com trial.medpath.com/clinical-trial/4789113888a9406c/nct00992173-phase-2b-study-ultracrace-iobenguane-neuroblastoma

Efficacy and Safety of Ultratrace™ Iobenguane I 131 in ... The primary purpose of the study is to determine if Ultratrace iobenguane I 131 can be used to successfully treat high-risk neuroblastoma. The study will also ...