Iobenguane (131-I) + Vorinostat for Neuroblastoma

(OPTIMUM Trial)

Recruiting at 20 trial locations

Overseen By Suzanne Bissonnette

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jubilant DraxImage Inc.

Must not be taking: Valproic acid, QT prolonging drugs

Disqualifiers: Pregnancy, Breastfeeding, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a combination of a radioactive drug and a cancer-fighting pill in patients with a specific type of neuroblastoma that hasn't responded well to other treatments. The radioactive drug kills cancer cells, and the pill makes them more vulnerable to the drug.

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.

What data supports the effectiveness of the drug combination Iobenguane (131-I) and Vorinostat for treating neuroblastoma?

Research shows that 131I-MIBG is effective in treating neuroblastoma, especially in relapsed cases, with response rates ranging from 0% to 75%. Vorinostat, when combined with 131I-MIBG, may enhance the treatment's effectiveness due to its properties that make cancer cells more sensitive to radiation. ^{1 2 3 4 5}

Is the combination of Iobenguane (131-I) and Vorinostat safe for treating neuroblastoma?

Research shows that Iobenguane (131-I) is generally safe for treating neuroblastoma, even in high-risk cases, and Vorinostat is being studied for its potential to enhance this treatment. However, the combination's safety is still being evaluated, and more studies are needed to fully understand the risks. ^{1 2 4 5 6}

What makes the drug combination of Iobenguane (131-I) and Vorinostat unique for treating neuroblastoma?

This drug combination is unique because it uses Iobenguane (131-I), a radiopharmaceutical that targets neuroblastoma cells, together with Vorinostat, which enhances the effect of radiation by making cancer cells more sensitive to it. This approach aims to improve the effectiveness of treatment for relapsed or hard-to-treat neuroblastoma. ^{1 4 5 7 8}

Research Team

Melda Dolan

Principal Investigator

Jubilant DraxImage Inc., dba Jubilant Radiopharma

Eligibility Criteria

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 undergone total body irradiation.

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

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

Trial Timeline

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

Treatment Details

Interventions

• 131I-MIBG (Radioactive Agent)
• Vorinostat (Histone Deacetylase Inhibitor)

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.

Participant Groups

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

131I-MIBG + Vorinostat

Group II: 131I-MIBG Experimental Treatment 1 Intervention

131I-MIBG

Who Is Running the Clinical Trial?

Jubilant DraxImage Inc.

Lead Sponsor

Trials

5

Recruited

15,900+

Findings from Research

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]

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 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]

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]

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]

References

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

Upfront consolidation treatment with 131I-mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma. [2022]

2. England 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. [2017]

3. England pubmed.ncbi.nlm.nih.gov

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. [2022]

4. United States 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. [2022]

5. United States 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. [2018]

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

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

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

Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. [2013]

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

Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and topotecan. [2015]