Protocol Summary

Protocol No.: OCR14309

Sponsor Protocol No.: ANBL1232

Study Title
Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High-Risk Neuroblastoma

Principal Investigator(s)
Slayton, William

Objective
This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.

Description
Group A (clinical observation)
Patients undergo clinical observation for 96 weeks in the absence of disease progression.

Group B (clinical observation, first-line chemotherapy)
Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin IV over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a PR or better is achieved, patients undergo clinical observation for 3 years.

Group C (clinical observation, first-line chemotherapy)
Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years.

Phase: Phase III (Cancer Control)

Age Group: Children

Scope: National

Treatment
Group A:
Observation

Group B:
Observation + First-line chemotherapy

Group C:
Observation + First-line chemotherapy

Detailed Eligibility
Inclusion Criteria:
1. Age Age 2. Enrollment on ANBL00B1 is required for all newly diagnosed patients
3. Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma or MYCN non-amplified ganglioneuroblastoma verified by histology
4. Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
- "Favorable" genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
- "Unfavorable" genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
- Only patients with MYCN non-amplified tumors are eligible for this study
5. Group A: patients - Greatest tumor diameter - Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
- No prior tumor resection or biopsy
6. Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
- Group A1:
- > 6 months and - Patients less than 6 months of age with an adrenal primary tumor > 3.1 and - - Group A2: =7. Group B: patients - No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.])
- No prior tumor resection, tumor biopsy ONLY
- Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1
8. Group C: patients 9. No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
10. All patients and/or their parents or legal guardians must sign a written informed consent
11. All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

EXCLUSION CRITERIA:
1. Patients with MYCN amplified tumors are not eligible
2. Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
3. Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study

Applicable Disease Sites
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02176967