Standardized Protocol of Surgery and Radiation for Patients With Brain Metastases in Relapsed Neuroblastoma

Study Overview
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Brief Summary
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HITC001 is a single institution study to evaluate the efficacy of using a standardized protocol of surgery and radiation for patients with brain metastases in relapsed neuroblastoma.

Detailed Description
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This clinical trial aims to establish a standardized protocol consisting of surgery and radiation for patients with brain metastases in relapsed neuroblastoma. This will be an adjunct study to NMTRC009 onto which patients will be enrolled to for treatment with precision therapy. This study will follow the efficacy, safety, and CNS progression-free survival of surgery and radiation.

Official Title
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A Standardized Protocol of Surgery and Radiation for Patients With Brain Metastases in Relapsed Neuroblastoma

Conditions
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Relapsed Neuroblastoma

Intervention / Treatment
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* Radiation: Cerebral Spinal (CS) radiation
* Radiation: Focal radiotherapy (SRS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≤ 21 years at the time of study entry. Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma. Disease Status: Patients must have ONE of the following along with disease in the CNS: Any episode of recurrent disease following completion of aggressive multi-drug frontline therapy. Any episode of progressive disease during aggressive multi-drug frontline therapy. Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocols. Measurable or evaluable disease by Brain MRI. Current disease state must be one for which there is currently no known curative therapy. Meet all inclusion criteria for study NMTRC009 Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines Exclusion Criteria: Meets all exclusion criteria for study NMTRC009 Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

Ages Eligible for Study
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Maximum Age: 21 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ≥ 5 years of age<br>Cerebral Spinal (CS) radiation | Radiation: Cerebral Spinal (CS) radiation<br>* Surgery plus Cerebral Spinal (CS) radiation<br>|
| Experimental: < 5 yo and ≥ 3 yo and CSF +<br>Cerebral Spinal (CS) radiation | Radiation: Cerebral Spinal (CS) radiation<br>* Surgery plus Cerebral Spinal (CS) radiation<br>|
| Experimental: All < 3 yo & < 5 yo/≥ 3 yo CSF neg<br>Focal radiotherapy (SRS) | Radiation: Focal radiotherapy (SRS)<br>* Surgery plus focal radiotherapy (stereotactic radiosurgery to the tumor bed [SRS])<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of Participants by the presence of radiologically measurable CNS disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans and/or CSF Sampling. | To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety | To determine the safety of using a standardized protocol of surgery and radiation for patients with brain metastases in relapse neuroblastoma | 3 years | 
| Progression Free Survival (PFS) interval for CNS lesions will be measured by days from start of treatment (surgery/radiation) to the date of any future progressive disease (PD) in CNS lesions per RESIST criteria. | Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements | 3 years | 
| Length of time that participants experience Overall Survival (OS) | Overall survival (OS) will be defined as the period in days from the date of enrollment until the date of death. | 8 years |