MIBG + Dinutuximab Therapy for Neuroblastoma

No longer recruiting at 11 trial locations

Overseen By Araz Marachelian, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: New Approaches to Neuroblastoma Therapy Consortium

Must not be taking: QTc prolonging, Valproic acid

Disqualifiers: Pregnancy, Organ transplant, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for children with neuroblastoma, a cancer that forms in certain nerve tissues. The study tests the effectiveness of a mix of 131I-MIBG (a radiopharmaceutical therapy) and dinutuximab (a monoclonal antibody therapy), with the potential addition of vorinostat. The goal is to determine the safest and most effective dose for future use. Children with high-risk neuroblastoma not fully controlled by other treatments might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy combination.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications that interfere with MIBG uptake, prolong QTc, or include valproic acid (for Part B) are not allowed. It's best to discuss your current medications with the study team.

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

Studies have shown that the combination of 131I-MIBG and dinutuximab is generally well-tolerated in patients with neuroblastoma that has returned or is resistant to treatment. Promising signs indicate that this treatment works against the cancer.

Adding vorinostat may enhance the treatment's effectiveness. However, researchers are still collecting safety information about this combination. As this is an early-phase trial, the focus is on determining the right dose that patients can handle safely. Detailed information on side effects is limited, but patients will be monitored closely to ensure safety.

These treatments have been used in other contexts and appear somewhat safe, but more research is needed to fully understand how well patients tolerate this specific combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using 131I-MIBG combined with Dinutuximab for treating neuroblastoma because this approach targets cancer cells in a highly specific way. Unlike standard therapies like chemotherapy or radiation, which can affect both healthy and cancerous cells, 131I-MIBG delivers radiation directly to neuroblastoma cells, potentially reducing side effects. Additionally, Dinutuximab is an antibody that helps the immune system attack cancer cells more effectively. This combination offers a two-pronged attack: directly targeting cancer cells with radiation and boosting the body's immune response, providing a promising new direction for treating this challenging childhood cancer.

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

Research has shown that 131I-MIBG effectively treats neuroblastoma, particularly when the cancer returns or resists other treatments. In this trial, participants will receive 131I-MIBG combined with dinutuximab, which studies indicate is generally well-tolerated and positively affects tumors. Some participants will also receive vorinostat, as evidence suggests that adding vorinostat to this combination might enhance the treatment's effectiveness. The radiation from 131I-MIBG and the action of the antibody dinutuximab can strengthen each other's effects. Overall, these treatments offer hope for better outcomes in challenging neuroblastoma cases. ^{1 2 5 6 7}

Who Is on the Research Team?

Thomas Cash, MD

Principal Investigator

Children's Healthcare of Atlanta

Araz Marachelian, MD, MS

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for pediatric patients with high-risk neuroblastoma, a type of cancer. They must have evidence of MIBG uptake in tumors or increased urinary catecholamines and meet specific criteria regarding their disease state (recurrent/progressive, refractory, persistent). Participants need to be recovered from prior treatments and have adequate organ function. Pregnant individuals or those unable to follow the study plan are excluded.

Inclusion Criteria

My cancer shows MIBG uptake in at least one site, confirmed within the last 28 days.

I have been diagnosed with neuroblastoma confirmed by tests.

My neuroblastoma is classified as high-risk according to COG.

Exclusion Criteria

I am currently receiving hemodialysis.

I have chosen not to participate in the NANT 2004-05 study.

I have had anti-GD2 therapy but not with 131I-MIBG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 131I-MIBG, dinutuximab, and GM-CSF, with optional vorinostat in Cohort B

8 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 months

What Are the Treatments Tested in This Trial?

Interventions

• 131I-MIBG
• Dinutuximab
• Vorinostat

Trial Overview The trial tests a combination therapy using 131I-MIBG with dinutuximab for children with neuroblastoma that's resistant or has come back after treatment. If safe, vorinostat will be added at a certain dose level. The study uses a 'rolling 6' design to find the best dose for phase 2 trials and includes additional patient groups to confirm findings.

How Is the Trial Designed?

Group I: Cohort B DL4 Experimental Treatment 5 Interventions

Vorinostat will be given on days 0-13 at 180 mg/m2/dose. Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group II: Cohort A DL3 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group III: Cohort A DL2 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 15 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group IV: Cohort A DL1 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 12 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

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

Approved in United States as Azedra for:

• Pheochromocytoma
• Neuroblastoma

Approved in European Union as Iobenguane I-131 for:

• Neuroblastoma
• Pheochromocytoma
• Paraganglioma

Who Is Running the Clinical Trial?

New Approaches to Neuroblastoma Therapy Consortium

Lead Sponsor

Trials

19

Recruited

1,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

United Therapeutics

Industry Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

A study involving 24 high-risk neuroblastoma patients showed that using 131I-mIBG as part of the treatment regimen is feasible and tolerable, especially when combined with myeloablative chemotherapy and hematopoietic stem cell transplantation.

The treatment resulted in improved outcomes for patients who had a partial response before receiving 131I-mIBG, with some achieving complete or very good partial responses, highlighting the potential effectiveness of this approach in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront consolidation treatment with 131I-mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma. Feng, J., Cheng, FW., Leung, AW., et al.[2022]

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]

(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 involving 32 newly diagnosed stage 4 neuroblastoma patients demonstrated that upfront treatment with 131I-MIBG is feasible and can be administered within 2 weeks of diagnosis, with a response rate of 38% after this therapy.

Following myeloablative therapy and autologous stem cell rescue, the overall response rate for patients who received 131I-MIBG was 71%, significantly higher than the 36% response rate in the chemotherapy group, indicating that 131I-MIBG is an effective option in the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients. Kraal, KC., Bleeker, GM., van Eck-Smit, BL., et al.[2017]

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

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

131I-mIBG therapy in relapsed/refractory neuroblastoma The immunotherapy approach seems to be more effective in patients with low disease burden; in particular, according to the SIOPEN MIBG skeletal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03332667

Study Details | NCT03332667 | MIBG With Dinutuximab + 131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40549985/

Phase I Study of 131I-Metaiodobenzylguanidine ... - PubMed MIBG combined with dinutuximab was well tolerated with encouraging antitumor activity. Vorinostat added to this combination may augment responses.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.10038

Phase I study of 131I-MIBG with dinutuximab for patients ... Preclinical neuroblastoma studies show cooperative effects when radiation is combined with anti-GD2 monoclonal antibody (mAb). We ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03332667/

Clinical Trial - MIBG With Dinutuximab + 131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease.

6. childrenshospital.org childrenshospital.org/clinical-trials/nct03332667

MIBG With Dinutuximab +/- Vorinostat 131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease.

7. cancer.gov cancer.gov/clinicaltrials/NCI-2018-01160

MIBG With Dinutuximab +/- Vorinostat - NCI 131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease.