Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02176967




Registration number
NCT02176967
Ethics application status
Date submitted
26/06/2014
Date registered
27/06/2014
Date last updated
24/11/2023

Titles & IDs
Public title
Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
Scientific title
Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-High-Risk Neuroblastoma
Secondary ID [1] 0 0
NCI-2014-00677
Secondary ID [2] 0 0
ANBL1232
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ganglioneuroblastoma 0 0
Localized Resectable Neuroblastoma 0 0
Localized Unresectable Neuroblastoma 0 0
Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biopsy
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Treatment: Drugs - Carboplatin
Other interventions - Clinical Observation
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Ultrasound

Experimental: Group A (clinical observation) - Patients undergo clinical observation for 96 weeks in the absence of disease progression. Patients also undergo CT, MRI, and/or ultrasound throughout the trial.

Experimental: 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. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.

Experimental: 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. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.


Treatment: Surgery: Biopsy
Undergo biopsy

Treatment: Surgery: Bone Marrow Aspiration
Undergo bone marrow aspiration

Treatment: Surgery: Bone Marrow Biopsy
Undergo bone marrow biopsy

Treatment: Drugs: Carboplatin
Given IV

Other interventions: Clinical Observation
Undergo clinical observation

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Surgery: Ultrasound
Undergo ultrasound
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) (Strata 1-4)
Timepoint [1] 0 0
From date of enrollment until death or last contact, assessed up to 3 years

Eligibility
Key inclusion criteria
- 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 or APEC14B1 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.]); horner syndrome is not considered neurologic compromise

- 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
or APEC14B1

- 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
Minimum age
No limit
Maximum age
18 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/08/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2026
Actual
Sample size
Target
621
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [6] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [7] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
6008 - Perth
Recruitment postcode(s) [7] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
Country [12] 0 0
United States of America
State/province [12] 0 0
Hawaii
Country [13] 0 0
United States of America
State/province [13] 0 0
Idaho
Country [14] 0 0
United States of America
State/province [14] 0 0
Illinois
Country [15] 0 0
United States of America
State/province [15] 0 0
Indiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Iowa
Country [17] 0 0
United States of America
State/province [17] 0 0
Kentucky
Country [18] 0 0
United States of America
State/province [18] 0 0
Louisiana
Country [19] 0 0
United States of America
State/province [19] 0 0
Maine
Country [20] 0 0
United States of America
State/province [20] 0 0
Maryland
Country [21] 0 0
United States of America
State/province [21] 0 0
Massachusetts
Country [22] 0 0
United States of America
State/province [22] 0 0
Michigan
Country [23] 0 0
United States of America
State/province [23] 0 0
Minnesota
Country [24] 0 0
United States of America
State/province [24] 0 0
Mississippi
Country [25] 0 0
United States of America
State/province [25] 0 0
Missouri
Country [26] 0 0
United States of America
State/province [26] 0 0
Nebraska
Country [27] 0 0
United States of America
State/province [27] 0 0
Nevada
Country [28] 0 0
United States of America
State/province [28] 0 0
New Hampshire
Country [29] 0 0
United States of America
State/province [29] 0 0
New Jersey
Country [30] 0 0
United States of America
State/province [30] 0 0
New Mexico
Country [31] 0 0
United States of America
State/province [31] 0 0
New York
Country [32] 0 0
United States of America
State/province [32] 0 0
North Carolina
Country [33] 0 0
United States of America
State/province [33] 0 0
North Dakota
Country [34] 0 0
United States of America
State/province [34] 0 0
Ohio
Country [35] 0 0
United States of America
State/province [35] 0 0
Oklahoma
Country [36] 0 0
United States of America
State/province [36] 0 0
Oregon
Country [37] 0 0
United States of America
State/province [37] 0 0
Pennsylvania
Country [38] 0 0
United States of America
State/province [38] 0 0
Rhode Island
Country [39] 0 0
United States of America
State/province [39] 0 0
South Carolina
Country [40] 0 0
United States of America
State/province [40] 0 0
South Dakota
Country [41] 0 0
United States of America
State/province [41] 0 0
Tennessee
Country [42] 0 0
United States of America
State/province [42] 0 0
Texas
Country [43] 0 0
United States of America
State/province [43] 0 0
Utah
Country [44] 0 0
United States of America
State/province [44] 0 0
Vermont
Country [45] 0 0
United States of America
State/province [45] 0 0
Virginia
Country [46] 0 0
United States of America
State/province [46] 0 0
Washington
Country [47] 0 0
United States of America
State/province [47] 0 0
West Virginia
Country [48] 0 0
United States of America
State/province [48] 0 0
Wisconsin
Country [49] 0 0
Canada
State/province [49] 0 0
Alberta
Country [50] 0 0
Canada
State/province [50] 0 0
British Columbia
Country [51] 0 0
Canada
State/province [51] 0 0
Manitoba
Country [52] 0 0
Canada
State/province [52] 0 0
Newfoundland and Labrador
Country [53] 0 0
Canada
State/province [53] 0 0
Nova Scotia
Country [54] 0 0
Canada
State/province [54] 0 0
Ontario
Country [55] 0 0
Canada
State/province [55] 0 0
Quebec
Country [56] 0 0
Canada
State/province [56] 0 0
Saskatchewan
Country [57] 0 0
New Zealand
State/province [57] 0 0
Auckland
Country [58] 0 0
New Zealand
State/province [58] 0 0
Christchurch
Country [59] 0 0
Puerto Rico
State/province [59] 0 0
San Juan
Country [60] 0 0
Saudi Arabia
State/province [60] 0 0
Riyadh

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02176967
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Holly J Meany
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02176967