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Summary

Eligibility
for people ages up to 17 months
Location
at Oakland, California and other locations
Dates
study started
Principal Investigator
Carla B. Golden

Description

Summary

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.

Official Title

Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-high-risk Neuroblastoma

Details

PRIMARY OBJECTIVES:

I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.

II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.

III. To achieve a 3-year OS of> 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.

SECONDARY OBJECTIVES:

I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.

II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.

III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.

IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.

V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.

VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.

VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.

OUTLINE: Patients are assigned to 1 of 3 treatment groups.

GROUP A: Patients undergo clinical observation for 96 weeks in the absence disease progression.

GROUP B: 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 intravenously (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 partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.

GROUP C: 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.

After completion of study treatment, patients are followed up annually for 5 years.

Keywords

Ganglioneuroblastoma Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Recurrent Neuroblastoma Regional Neuroblastoma Stage 4 Neuroblastoma Cyclophosphamide Liposomal doxorubicin Etoposide phosphate Carboplatin Doxorubicin Etoposide

Eligibility

You can join if…

Open to people ages up to 17 months

  • Patients must be:
  • < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
  • < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
  • Enrollment on ANBL00B1 is required for all newly diagnosed patients
  • Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
  • 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
  • Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
  • Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
  • 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
  • Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
  • Group A1:
  • 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR

  • Patients less than 6 months of age with an adrenal primary tumor> 3.1 and <5 cm in greatest diameter OR
  • < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
  • Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
  • Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
  • 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
  • Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
  • No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute(NCI) requirements for human studies must be met

You CAN'T join if...

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

Locations

  • Children's Hospital Central California accepting new patients
    Madera, California, 93636-8762, United States
  • Lucile Packard Children's Hospital Stanford University accepting new patients
    Palo Alto, California, 94304, United States
  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento, California, 95817, United States
  • Sutter General Hospital accepting new patients
    Sacramento, California, 95816, United States
  • Children's Hospital Los Angeles accepting new patients
    Los Angeles, California, 90027, United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte, California, 91010, United States
  • Southern California Permanente Medical Group accepting new patients
    Downey, California, 90242, United States
  • Childrens Hospital of Orange County accepting new patients
    Orange, California, 92868, United States
  • Loma Linda University Medical Center accepting new patients
    Loma Linda, California, 92354, United States
  • Nevada Cancer Research Foundation CCOP accepting new patients
    Las Vegas, Nevada, 89106, United States
  • Sunrise Hospital and Medical Center accepting new patients
    Las Vegas, Nevada, 89109, United States

Details

Status
accepting new patients
Start Date
Sponsor
Children's Oncology Group
ID
NCT02176967
Phase
Phase 3
Lead Scientist
Carla B. Golden
Study Type
Interventional
Last Updated
September 1, 2016