131I-MIBG Alone VS. 131I-MIBG With Vincristine and Irinotecan VS131I-MIBG With Vorinostat

Study Overview
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Brief Summary
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This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.

Official Title
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NANT 2011- 01: Randomized Phase II Pick the Winner Study of 131I-MIBG, 131I-MIBG With Vincristine and Irinotecan, or 131I-MIBG With Vorinostat for Resistant/Relapsed Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Radiation: 131I-MIBG
* Drug: Vincristine
* Drug: Irinotecan
* Drug: Vorinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be > 24 months and < 30 years of age when registered on study. Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with > 3 residual lesions on end-induction MIBG scan. Patients must have evidence of MIBG uptake into tumor at ≥ one site within 4 weeks prior to entry on study and subsequent to any intervening therapy. Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study. Patients must have a dose of unpurged peripheral blood stem cells is 2.0 x 106 viable CD34+ cells/kg available. Exclusion Criteria: They have had previous I-131 MIBG therapy They have other medical problems that could get much worse with this treatment. They are pregnant or breast feeding. They have a history of a venous or arterial thrombosis that was not associated to a central line. They have active infections such as hepatitis or fungal infections. They have active diarrhea. They have had an allogeneic stem cell transplant (received stem cell from someone else) They can't cooperate with the special precautions that are needed for this trial.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single-Agent 131I-MIBG<br>Single-agent 131I-MIBG (Arm A) 18 mCi/kg 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15. | Radiation: 131I-MIBG<br> <br> * Other names: MIBG;|
| Active Comparator: 131I-MIBG with Vincristine/Irinotecan<br>Vincristine / irinotecan / 131I-MIBG (Arm B): vincristine 2 mg/m2 (maximum dose 2 mg) intravenously on Day 0; irinotecan 50 mg/m2 (maximum dose 100 mg) intravenously on Days 0 to 4. Patients will also receive diarrhea prophylaxis with cefixime 8 mg/kg/day orally on Days -1 to +6. 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15. | Radiation: 131I-MIBG<br> <br> * Other names: MIBG;Drug: Vincristine<br> <br> Drug: Irinotecan<br> <br> |
| Active Comparator: 131I-MIBG with Vorinostat<br>Vorinostat / 131I-MIBG (Arm C); vorinostat 180 mg/m2 (maximum dose 400 mg) orally once daily on Days -1 to +12 (14 total doses). 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15. | Radiation: 131I-MIBG<br> <br> * Other names: MIBG;Drug: Vorinostat<br> <br> * Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response After One Course of Therapy | To identify the MIBG treatment regimen associated with the highest overall response rate after one course of treatment on the three arms. The response evaluation was based on central review (intent to treat analysis). Responders defined as meeting CR/MRD/PR criteria. Response was based on NANT response criteria v1.2 (https://doi.org/10.1002/pbc.26940). RECST 1.1 criteria was used for measurable tumors with PR criteria > 30% decrease in target tumor size. Curie score was used with PR criteria > 50% decrease in Curie score. Complete Response- disappearance of all target lesions, Curie score of 0 and no detectable bone marrow disease. Overall Response (OR)=CR+PR. | 43-50 days from study day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 or Greater Non-hematologic Toxicities | Compare toxicity profiles for grade 3 or greater toxicities associated with each of 131I-MIBG treatment regimens; single-agent 131I-MIBG; Vincristine/Irinotecan/131I-MIBG; or Vorinostat/131I-MIBG | All toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months |