MIBG + Vorinostat/Dinutuximab for Neuroblastoma
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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
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.12345Why 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.46789
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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive a single course of treatment with 131I-MIBG combined with either vorinostat, dinutuximab, or both, depending on the assigned arm
Disease Evaluation
Disease evaluation occurs to assess the response to the treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
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
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?
3
Treatment groups
Experimental Treatment
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.
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.
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.
Find a Clinic Near You
Who Is Running the Clinical Trial?
New Approaches to Neuroblastoma Therapy Consortium
Lead Sponsor
United Therapeutics
Industry Sponsor
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
Citations
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, ...
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 ...
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.
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.
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%,.
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 ...
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 ...
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 ...
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).
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