Radiation Therapy for Neuroblastoma

Recruiting at 1 trial location

Overseen By David Kozono, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Pregnancy, Breastfeeding, others

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

Compensation: Varies

Number of Visits: Unknown

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how radiation therapy treats tumors in cases of neuroblastoma and diffuse midline glioma. Researchers aim to understand the biological effects of radiation, including its benefits and side effects, by collecting and analyzing samples from patients before, during, and after treatment. The trial uses two treatments: 131I-Metaiodobenzylguanidine (MIBG), a form of targeted radiotherapy, and external beam radiotherapy. Ideal candidates for this trial are those diagnosed with high-risk neuroblastoma or diffuse midline glioma who have not received prior systemic or radiation therapy. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could improve future treatment options.

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, if you are on corticosteroids, you must be on a stable or decreasing dose for at least 3 days before a baseline MRI scan.

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

Research has shown that 131I-Metaiodobenzylguanidine (MIBG) is usually well-tolerated by patients with neuroblastoma, with about one-third responding positively. The main side effects involve blood-related issues, which can often be managed with extra care, making them typically manageable.

Studies indicate that external beam radiotherapy can improve outcomes for children with advanced neuroblastoma. Like many cancer treatments, it can affect nearby healthy tissues, but the overall benefits often outweigh these risks.

Both treatments have been well-studied and can be effective, with generally manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for neuroblastoma because they offer a new approach compared to traditional therapies like chemotherapy and surgery. 131I-Metaiodobenzylguanidine (MIBG) is unique because it uses a radioactive compound that targets neuroblastoma cells specifically, delivering radiation directly to the cancer cells while sparing healthy tissue. This targeted approach can potentially reduce side effects and improve effectiveness. Additionally, external beam radiotherapy provides another method of delivering precise doses of radiation to the tumor, further minimizing damage to surrounding healthy tissues. These innovative treatments could lead to better outcomes for patients with high-risk neuroblastoma.

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

Research has shown that 131I-Metaiodobenzylguanidine (MIBG) therapy, one of the treatments in this trial, can effectively treat neuroblastoma. Studies indicate that about one-third of patients experience positive results, with some achieving complete remission. The objective tumor response rate, which measures how often tumors shrink or disappear, averages around 32%, with some studies reporting rates as high as 48%.

External beam radiotherapy (EBRT) is another treatment option in this trial for high-risk neuroblastoma. It has improved outcomes, particularly in severe cases of stage 4 neuroblastoma. While success rates vary, EBRT has proven valuable in managing this condition, offering a survival advantage in some cases. ^{3 4 6 7 8}

Who Is on the Research Team?

David E. Kozono

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults with specific types of brain tumors or high-risk neuroblastoma. Participants must meet certain age, health, and diagnostic criteria, have stable vital functions, and not be pregnant or breastfeeding. They should also be enrolled in one of the specified clinical trials related to their condition.

Inclusion Criteria

My bone marrow, kidneys, liver, and nervous system are functioning well.

Availability of tumor tissue, blood and/or CSF biospecimens

I am aged 1-30 with a specific high-risk neuroblastoma and have not had certain treatments.

Exclusion Criteria

Inability to follow the procedures of the study

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive radiation therapy, including external beam radiation for DMG and 131I-MIBG radiopharmaceutical for neuroblastoma

Varies by individual treatment plan

Multiple visits for radiation sessions

Sample Collection

Collection of biospecimens including blood, CSF, and tumor samples before, during, and after radiation treatment

Concurrent with treatment phase

Follow-up

Participants are monitored for safety, effectiveness, and quality of life outcomes after treatment

Up to 3 years

Regular follow-up visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• 131I-Metaiodobenzylguanidine (MIBG)
• External beam radiotherapy

Trial Overview

The MCT aims to collect detailed biological data from patients undergoing radiation therapy for tumor treatment. It involves external beam radiotherapy and a radioactive drug called 131I-MIBG to understand how these treatments work against tumors while assessing potential side effects.

How Is the Trial Designed?

Group I: Neuroblastoma Experimental Treatment 1 Intervention

Subjects with high-risk neuroblastoma on COG ANBL1531 (NCT03126916) Arm B

Group II: Diffuse Midline Glioma Experimental Treatment 1 Intervention

Subjects with diffuse midline glioma on PNOC023 (NCT04732065) Arm A or B

131I-Metaiodobenzylguanidine (MIBG) is already approved in United States, European Union for the following indications:

Approved in United States as 131I-MIBG for:

• High-risk neuroblastoma

Approved in European Union as 131I-MIBG for:

• High-risk neuroblastoma

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 23 children and adolescents with metastatic neuroblastoma, I-metaiodobenzylguanidine (I-MIBG) showed a mean whole-body retention rate of 48% at 24 hours, indicating effective clearance and a half-life of 23 hours, which is important for understanding patient safety post-treatment.

The estimated maximum radiation dose to family caregivers was 1.88 mSv, while medical staff received a much lower dose of 43 μSv, highlighting the need for specific radiation safety measures to protect caregivers and healthcare providers during I-MIBG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric 131I-MIBG Therapy for Neuroblastoma: Whole-Body 131I-MIBG Clearance, Radiation Doses to Patients, Family Caregivers, Medical Staff, and Radiation Safety Measures. Willegaignon, J., Crema, KP., Oliveira, NC., et al.[2018]

A 14-month-old girl treated with iodine 131-metaiodobenzylguanidine ([(131)I]MIBG) for stage 4 neuroblastoma developed severe oral mucositis 14 days post-treatment, indicating a significant side effect of this targeted radiotherapy.

The accumulation of [(131)I]MIBG in the salivary glands, as seen in imaging, may be linked to sympathetic innervation, suggesting a mechanism for the observed oral side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe oral mucositis after therapeutic administration of [131I]MIBG in a child with neuroblastoma. Dahllöf, G., Borgström, P., Lundell, 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]

In a study of 76 heavily pretreated patients with relapsed neuroblastoma, early second treatment with (131) I-MIBG was found to be safe and effective, with 39% of patients experiencing a reduction in overall disease burden after two treatments.

The response rate to the second (131) I-MIBG infusion was 29%, and it was noted that patients who appeared to have a complete response on initial scans still had significant disease visible on subsequent imaging, suggesting the need for continued treatment even in cases of apparent remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tandem 131I-metaiodobenzylguanidine infusions in relapsed/refractory neuroblastoma. Johnson, K., McGlynn, B., Saggio, J., et al.[2013]

In a study of 25 patients with relapsed or refractory neuroblastoma, individualized dosimetry-based I-131 mIBG therapy resulted in a 58% overall response rate, indicating effective treatment outcomes.

Despite significant acute toxicities, such as grade 3/4 neutropenia and thrombocytopenia occurring in 82% and 71% of treatments respectively, these side effects were manageable and resolved with appropriate care, suggesting that the therapy can be safely administered with proper support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma. George, SL., Falzone, N., Chittenden, S., et al.[2018]

In a study involving 30 patients with relapsed neuroblastoma, treatment with 131I-MIBG showed a 37% response rate, indicating its potential effectiveness, especially at doses of 12 mCi/kg or higher.

The treatment was associated with significant hematologic toxicity, particularly thrombocytopenia and neutropenia, but these effects could be managed with autologous bone marrow support, suggesting a safer application in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. Matthay, KK., DeSantes, K., Hasegawa, B., et al.[2022]

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 trial involving 105 patients with relapsed or refractory neuroblastoma, the combination of vorinostat and MIBG showed the highest response rate (32%) compared to MIBG alone (14%) and MIBG with vincristine and irinotecan (14%).

The study indicated that while vorinostat combined with MIBG had manageable toxicity, the vincristine and irinotecan combination did not enhance the response rate and was associated with higher toxicity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of MIBG Versus MIBG, Vincristine, and Irinotecan Versus MIBG and Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A Report From NANT Consortium. DuBois, SG., Granger, MM., Groshen, S., et al.[2022]

In a study of 111 stage 4 neuroblastoma patients, those who received (131)I-MIBG therapy showed better 3-year event-free survival (46%) and overall survival (58%) compared to those who did not receive the therapy (19% and 43%, respectively).

However, when analyzing patients who underwent high-dose chemotherapy with autologous stem cell transplantation, the outcomes were similar regardless of (131)I-MIBG therapy, indicating that the benefits of (131)I-MIBG may be overshadowed by the effects of ASCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. Schmidt, M., Simon, T., Hero, B., et al.[2022]

Citations

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sciencedirect.com

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Studies show that [ 131 I]mIBG therapy can be an effective treatment in one-third of patients with acceptable toxicity.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12002777/

131I-mIBG therapy in relapsed/refractory neuroblastoma

Complete metabolic remission was achieved in 2 out of 23 (9%, 95% CI 1% to 28%) with positive mIBG on bone and in 3 out of 20 (15%, 95% CI 3% to ...

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bmccancer.biomedcentral.com

bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09329-2

The efficacy and safety of Iodine-131 ... - BMC Cancer

131 I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma.

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A systematic review of 131I-meta iodobenzylguanidine ...

The objective tumour response rate reported in 25 studies ranged from 0% to 75%, mean 32%. We conclude that (131)I-mIBG is an active treatment ...

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esmoopen.com

esmoopen.com/article/S2059-7029(25)00410-7/pdf

131I-mIBG therapy in relapsed/refractory neuroblastoma

In this scenario, our data indicate that mIBG therapy may be considered a suitable bridge option to reduce the tumour burden with an ORR of 48%,.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9150928/

A Safety and Feasibility Trial of 131I-MIBG in Newly ...

Early phase trials of 131I-MIBG in relapsed/refractory neuroblastoma showed response rates up to 37% with dose-limiting hematologic toxicity abrogated by ASCR.

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esmoopen.com

esmoopen.com/article/S2059-7029(25)00410-7/fulltext

131I-mIBG therapy in relapsed/refractory neuroblastoma

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

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jnm.snmjournals.org

jnm.snmjournals.org/content/jnumed/early/2023/02/02/jnumed.122.264775.full.pdf

Efficacy and safety of 124I-mIBG dosimetry-guided high ...

QUESTION: Is 124I-mIBG dosimetry guided high-activity 131I-mIBG therapy of advanced pheochromocytoma or neuroblastoma effective and safe?