MIBG + Vorinostat/Dinutuximab for Neuroblastoma

Not yet recruiting at 12 trial locations

Overseen By Araz Marachelian, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New Approaches to Neuroblastoma Therapy Consortium

Must not be taking: Anti-GD2, Vorinostat

Disqualifiers: Pregnancy, Organ transplant, HIV, 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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for high-risk neuroblastoma, a cancer that mostly affects children. Participants will be divided into three groups, each receiving a different combination of treatments: 131I-MIBG (a type of radiotherapy) with either vorinostat (a histone deacetylase inhibitor), dinutuximab (an antibody therapy), or both. The goal is to determine which combination best treats the cancer. Individuals with high-risk neuroblastoma who have experienced previous disease progression or specific treatment responses might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that 131I-MIBG, a treatment for neuroblastoma, has been used in over 100 children in the U.S. for recurrent cases. It effectively combats the disease and is generally well-tolerated, with manageable side effects.

Dinutuximab, another treatment in this trial, can cause serious side effects like severe pain and nerve damage in many patients. However, it significantly lowers the risk of death from neuroblastoma.

Vorinostat, approved for another type of cancer, commonly causes fatigue and nausea. Studies in neuroblastoma suggest it works well with other treatments, though it can cause some discomfort.

Overall, while these treatments are generally safe and effective, some can cause significant discomfort. Considering these effects is important when deciding to participate in a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuroblastoma because they combine advanced therapies to tackle the disease more effectively. Unlike the standard of care, which often involves chemotherapy and radiation, these investigational treatments use 131I-MIBG, a targeted radiotherapy that delivers radiation directly to cancer cells, minimizing damage to healthy tissues. Additionally, the combination of vorinostat and dinutuximab introduces new mechanisms: vorinostat is a histone deacetylase inhibitor that can alter gene expression to stop cancer growth, while dinutuximab is an antibody that specifically targets neuroblastoma cells. These innovative approaches aim to improve outcomes for patients by enhancing the precision and efficacy of treatment.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various therapy combinations for neuroblastoma. Previous studies have shown that a treatment called 131I-MIBG holds promise for neuroblastoma, with about one-third of patients responding well. In Arm B, 131I-MIBG combines with dinutuximab, which has increased the success rate to up to 60% in some cases. Arm A will test 131I-MIBG with vorinostat, which might enhance the treatment's impact. Arm C will evaluate the combination of all three drugs: 131I-MIBG, dinutuximab, and vorinostat, as research suggests that using all three together could lead to better results. Overall, these combinations aim to improve outcomes for those with hard-to-treat neuroblastoma. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 1-29 with high-risk neuroblastoma or ganglioneuroblastoma nodular subtype, showing MIBG uptake in tumors. They must have a history of recurrent, refractory, or persistent disease and meet specific organ function requirements. Pregnant individuals, those unable to follow the study protocol, with major organ system disease, prior allogeneic stem cell transplant or certain infections are excluded.

Inclusion Criteria

My cancer shows MIBG uptake in at least one site.

My neuroblastoma has come back, hasn't responded, or hasn't gone away.

I am between 1 and 29 years old.

Exclusion Criteria

Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.

Patients who may not be able to comply with the safety monitoring or radiation isolation requirements of the study.

My major organs are healthy enough to handle treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single course of treatment with 131I-MIBG combined with either vorinostat, dinutuximab, or both, depending on the assigned arm

8 weeks

Multiple visits for drug administration and monitoring

Disease Evaluation

Disease evaluation occurs to assess the response to the treatment

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Optional Second Course

Participants may choose to proceed to a second course of the same treatment if they and their physician feel healthy enough to do so

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 131I-MIBG
• Dinutuximab
• Vorinostat

Trial Overview The trial tests three treatments for neuroblastoma: Arm A gets one course of radiation therapy (131I-MIBG) with vorinostat; Arm B receives 131I-MIBG and dinutuximab; Arm C combines all three (131I-MIBG, dinutuximab + vorinostat). Patients may opt for a second course if deemed healthy enough.

How Is the Trial Designed?

Group I: Arm C: 131I-MIBG + vorinostat + dinutuximab Experimental Treatment 3 Interventions

Patients assigned to Arm C will receive vorinostat 180 mg/m2/dose (maximum dose 400 mg) on Days 0 to 13, 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1. Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Group II: Arm B: 131I-MIBG + dinutuximab Experimental Treatment 2 Interventions

Patients assigned to Arm B will receive 18 mCi/kg (maximum dose 1200 mCi) 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15 (+2/-1 days). Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Group III: Arm A: 131I-MIBG + vorinostat Experimental Treatment 2 Interventions

Patients assigned to Arm A will receive vorinostat orally once daily on Days 0 to 13 at a dose of 180 mg/m2/dose (maximum dose 400 mg). Patients will receive 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1 and autologous stem cell infusion on Day 15 (plus 2 days or minus 1 day, hereafter abbreviated as +2/-1 days). There must be at least 24 hours between the last dose of vorinostat and stem cell infusion. Disease evaluation is to occur between days 50-60. The time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Who Is Running the Clinical Trial?

New Approaches to Neuroblastoma Therapy Consortium

Lead Sponsor

Trials

19

Recruited

1,700+

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

Jubilant DraxImage Inc.

Industry Sponsor

Trials

5

Recruited

15,900+

Citations

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

Phase I study of 131I-MIBG with dinutuximab for patients ... Among 26 response-evaluable patients, the centrally-confirmed response rate was 31% across all dose levels: 2/6 (33%) in DL1, 3/5 (60%) in DL2, ...

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

131I-mIBG therapy in relapsed/refractory neuroblastoma The 3-year overall survival was 55% (95% CI 33% to 73%) and event-free survival was 42% (95% CI 23% to 60%). Conclusion. The 131I-mIBG therapy ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000187

A narrative review of 35 years of meta-[131I] ... Studies show that [ 131 I]mIBG therapy can be an effective treatment in one-third of patients with acceptable toxicity.

4. 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.

5. 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 ... MIBG labeled with iodine-131 (131I-MIBG) has activity against relapsed and newly diagnosed neuroblastoma. Early phase trials of 131I-MIBG in relapsed/refractory ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01163383

Study Details | NCT01163383 | 131-I-MIBG Therapy for ... 131I-MIBG is experimental, but has been used in more than 100 children in the United States by itself to treat relapsed neuroblastoma. A recent study using ...

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

131I-mIBG therapy in relapsed/refractory neuroblastoma I-mIBG plus melphalan, supported by autologous haematopoietic stem cell rescue, is a safe treatment in R/R NB. •. Molecular radiotherapy needs ...

9. jnm.snmjournals.org jnm.snmjournals.org/content/53/7/1155

Dose Escalation Study of No-Carrier-Added 131I ... We have shown that NCA 131I-MIBG is tolerable and feasible at a dose of 666 MBq/kg, equal to the recommended dose with carrier-added MIBG (8).