Iobenguane (131-I) + Vorinostat for Neuroblastoma

(OPTIMUM Trial)

Not currently recruiting at 21 trial locations

Overseen By Melda Dolan, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Jubilant DraxImage Inc.

Must not be taking: Valproic acid, QT prolonging drugs

Disqualifiers: Pregnancy, Breastfeeding, 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: Unknown

Duration: 16-26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, 131I-MIBG (a type of radiopharmaceutical therapy) and Vorinostat (a type of histone deacetylase inhibitor), to evaluate their effectiveness for people with neuroblastoma, a type of cancer that has returned or is worsening. The goal is to determine if this combination can effectively treat the cancer and ensure patient safety. It suits those previously treated for neuroblastoma with tumors visible on specific scans. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take valproic acid within 30 days of starting the study, and you should not be on medications that prolong the QT interval when you begin the trial.

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

Research has shown that 131I-MIBG is generally safe and well-tolerated. In studies with newly diagnosed children, it was well-tolerated. However, common side effects, such as low blood platelet counts and low white blood cell counts, occurred in about 79% and 78% of cases, respectively, increasing the risk of bleeding or infection.

When combined with Vorinostat, research indicates that 131I-MIBG can effectively treat neuroblastoma, with manageable side effects. No major safety concerns have been widely reported for this combination, suggesting it could be a promising option for those considering a new treatment for neuroblastoma. Patients should consult their healthcare provider to understand what these findings might mean for them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of 131I-MIBG and Vorinostat for treating neuroblastoma because it offers a novel approach to tackling this aggressive cancer. Unlike standard treatments such as chemotherapy and surgery, 131I-MIBG delivers targeted radiation directly to cancer cells, potentially reducing damage to surrounding healthy tissue. Vorinostat, on the other hand, is a histone deacetylase inhibitor that can enhance the effectiveness of 131I-MIBG by making cancer cells more susceptible to radiation. This combination not only targets the cancer more precisely but also aims to improve treatment outcomes by attacking the disease on multiple fronts.

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

Research has shown that 131I-MIBG, one of the treatments in this trial, can help treat neuroblastoma, with some studies finding it effective in about one-third of patients. In one study, it shrank tumors in nearly half of the patients. When combined with other treatments, it has shown promise in managing the disease.

In this trial, researchers are testing Vorinostat as a partner to 131I-MIBG in one of the treatment arms to potentially increase its effectiveness. Early research suggests that this combination might lead to better results, but more information is needed for confirmation. Overall, 131I-MIBG alone has been effective, and adding Vorinostat could enhance its efficacy. ^{3 6 7 8 9}

Who Is on the Research Team?

Melda Dolan

Principal Investigator

Jubilant DraxImage Inc., dba Jubilant Radiopharma

Are You a Good Fit for This Trial?

This trial is for patients with high-risk neuroblastoma that's come back or gotten worse. They should have recovered from previous treatments, not exceeded a certain dose of 131I-MIBG therapy, and have specific organ functions within normal ranges. Patients must be over 1 year old, able to perform daily activities at least half the time (Karnofsky/Lansky score ≥50%), and agree to use effective contraception if applicable.

Inclusion Criteria

My scans show that my cancer takes up a specific dye.

I have had platelet transfusions but my current platelet count is above 50,000/μL without needing a transfusion for the last week.

My thyroid function is normal, or if not, it's not a major concern.

Exclusion Criteria

I have not taken valproic acid in the last 30 days.

I have undergone total body irradiation.

I am not taking any medications that affect my heart's rhythm and haven't taken Pentamidine in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive 131I-MIBG as a single agent or in combination with Vorinostat. The treatment phase lasts up to 26 weeks for two treatments or 16 weeks for one treatment.

16-26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments for disease progression and adverse events.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 131I-MIBG
• Vorinostat

Trial Overview The study tests how safe and effective the combination of two drugs, Iobenguane (131-I) and Vorinostat, is in treating recurrent or progressive high-risk neuroblastoma. It looks at whether this combo can help patients whose cancer has returned or continued to grow despite treatment.

How Is the Trial Designed?

Group I: 131I-MIBG + Vorinostat Experimental Treatment 1 Intervention

131I-MIBG + Vorinostat

Group II: 131I-MIBG Experimental Treatment 1 Intervention

131I-MIBG

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?

Jubilant DraxImage Inc.

Lead Sponsor

Trials

5

Recruited

15,900+

Published Research Related to This Trial

In a phase I study involving 27 patients with relapsed/refractory neuroblastoma, the combination of vorinostat and (131)I-MIBG was found to be tolerable, particularly at the dose of 180 mg/m² of vorinostat with 18 mCi/kg of MIBG, with manageable side effects like neutropenia and thrombocytopenia.

The study reported a response rate of 12% overall, increasing to 17% at the highest tolerated dose, indicating some efficacy of the combination treatment, and histone acetylation was successfully increased, suggesting the mechanism of action of vorinostat in enhancing the effects of MIBG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma. DuBois, SG., Groshen, S., Park, JR., et al.[2018]

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 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]

The study successfully combined (131)I-meta iodobenzylguanidine ((131)I-mIBG) therapy with the topoisomerase-1 inhibitor topotecan in eight children with relapsed stage IV neuroblastoma, demonstrating that this intensified treatment regimen is safe and feasible.

In vivo dosimetry was effectively used to deliver a precise total whole-body radiation dose of approximately 4 Gy, with satisfactory recovery of blood cell counts in all patients, indicating that this method can guide accurate dosing in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. Gaze, MN., Chang, YC., Flux, GD., et al.[2013]

The combination of (131)I-MIBG and topotecan showed a promising overall objective response rate of 57% in newly diagnosed high-risk neuroblastoma patients, indicating its efficacy as a treatment option.

This study involved 16 patients with a median age of 2.8 years, and it demonstrated that the combination therapy not only effectively targeted the primary tumor (94% response rate) but also had manageable hematologic toxicity, making it a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and topotecan. Kraal, KC., Tytgat, GA., van Eck-Smit, BL., et al.[2015]

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]

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]

(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]

Citations

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

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%, ...

2. 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.

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

The efficacy and safety of Iodine-131 ... - BMC Cancer In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5636618/

Improved outcome of 131I-mIBG treatment through ... Improved outcome of 131I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma · Abstract · Materials and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01163383

Study Details | NCT01163383 | 131-I-MIBG Therapy for ... A recent study using increasing doses of 131I-MIBG in both children and adults with relapsed neuroblastoma or metastatic pheochromocytoma/ganglioma showed anti- ...

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

A Safety and Feasibility Trial of 131I-MIBG in Newly ... This pilot trial demonstrated feasibility and tolerability of administering 131I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children ...

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

131I-mIBG therapy in relapsed/refractory neuroblastoma Data on demographics, disease status, previous treatment, 131I-mIBG treatment, antitumour activity, toxicity and safety of each patient treated ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.4_suppl.388

Pooled safety analysis of high-specific-activity I-131 MIBG ... Conclusions: HSA I-131 MIBG was safe and well-tolerated among subjects with iobenguane scan positive cancers. No trends were discerned between ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03561259

NCT03561259 | A Study of Therapeutic Iobenguane (131-I) ... The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination with Vorinostat in patients with Recurrent or Progressive ...