Radiation Therapy for Neuroblastoma

Recruiting at 1 trial location

Overseen by David E. Kozono

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Brigham and Women's Hospital

Disqualifiers: Pregnancy, Breastfeeding, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial collects biological samples from children with specific cancers who are receiving radiation therapy. The goal is to understand how radiation affects both cancerous and normal cells, which can help improve future treatments.

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.

What data supports the effectiveness of the treatment 131I-Metaiodobenzylguanidine (MIBG) for neuroblastoma?

Research shows that 131I-MIBG is an effective treatment for neuroblastoma, with response rates greater than 30% in patients with difficult-to-treat cases. It is considered safe, although it can cause some blood-related side effects. ^{1 2 3 4 5}

Is radiation therapy with 131I-MIBG safe for humans?

Radiation therapy with 131I-MIBG for neuroblastoma is generally considered safe, but it can cause side effects like myelosuppression (a decrease in bone marrow activity) and oral mucositis (painful inflammation and sores in the mouth). Safety measures are in place to protect patients, family caregivers, and medical staff from radiation exposure. ^{3 4 5 6 7}

How is the treatment 131I-MIBG with EBRT different from other treatments for neuroblastoma?

The treatment 131I-MIBG is unique because it specifically targets neuroblastoma cells, delivering radiation directly to the tumor, which may result in more effective and less toxic treatment compared to conventional external-beam radiotherapy. It is particularly used for patients with relapsed or refractory neuroblastoma, where other treatments may not be effective. ^{3 4 5 8 9}

Research Team

David E. Kozono

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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

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+

Findings from Research

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 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 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 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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma. [2018]

2. United States 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. [2022]

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

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

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

Safety and efficacy of tandem 131I-metaiodobenzylguanidine infusions in relapsed/refractory neuroblastoma. [2013]

5. 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]

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

Severe oral mucositis after therapeutic administration of [131I]MIBG in a child with neuroblastoma. [2013]

7. United States 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. [2018]

8. Germany 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. [2022]

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

Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. [2022]