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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00499616




Registration number
NCT00499616
Ethics application status
Date submitted
10/07/2007
Date registered
11/07/2007
Date last updated
6/07/2021

Titles & IDs
Public title
Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma
Scientific title
Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma
Secondary ID [1] 0 0
COG-ANBL0531
Secondary ID [2] 0 0
ANBL0531
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - carboplatin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - topotecan hydrochloride
Treatment: Drugs - Isotretinoin
Treatment: Surgery - Surgery
Treatment: Drugs - Filgrastim

Experimental: Group 2 (chemotherapy, surgery) - 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.

Experimental: Group 3 (chemotherapy, surgery) - 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

Experimental: Group 4 (chemotherapy, surgery, antineoplastic therapy) - 8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients \< 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

Experimental: Non-intermediate risk enrolled on intermediate risk trial - The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.


Treatment: Drugs: carboplatin
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: doxorubicin hydrochloride
Given IV

Treatment: Drugs: etoposide
Given orally

Treatment: Drugs: topotecan hydrochloride
Given IV

Treatment: Drugs: Isotretinoin
Given orally

Treatment: Surgery: Surgery
With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

Treatment: Drugs: Filgrastim
Administered subcutaneously or by IV beginning 24-48 hrs after the last dose of chemotherapy \& continuing daily until the ANC is greater than or equal to 1500 following the myelosuppressive nadir . Supportive care given to stimulate neutrophil recovery following chemotherapy and to shorten the duration of chemotherapy-induced neutropenia. On ANBL0531 the use of filgrastim was required for patients less than 60 days of age and was optional for other patients.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) Rates
Timepoint [1] 0 0
3 years
Primary outcome [2] 0 0
Definitive Determination of the Prognostic Ability of 1p and 11q
Timepoint [2] 0 0
At baseline
Primary outcome [3] 0 0
Comparison Between Reduce Intensity of Therapy for Patients With Stage 4 Neuroblastoma and Favorable Biological Features and Patients < 1 Year of Age With Stage 4 Neuroblastoma Treated on COG-A3961
Timepoint [3] 0 0
Up to 3 years
Primary outcome [4] 0 0
Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961
Timepoint [4] 0 0
Up to 3 years
Primary outcome [5] 0 0
Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma
Timepoint [5] 0 0
Up to 3 years
Primary outcome [6] 0 0
Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment
Timepoint [6] 0 0
From baseline to up to 10 years
Primary outcome [7] 0 0
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)
Timepoint [7] 0 0
Up to 10 years
Primary outcome [8] 0 0
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates
Timepoint [8] 0 0
Up to 10 years
Primary outcome [9] 0 0
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate
Timepoint [9] 0 0
Up to 10 years
Secondary outcome [1] 0 0
Second-event-free Survival (E2FS)
Timepoint [1] 0 0
From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse, progressive disease, secondary malignancy, or death; up to 3 years
Secondary outcome [2] 0 0
Second-Overall Survival
Timepoint [2] 0 0
From the time of the first progressive, non-metastatic event; up to 3 years
Secondary outcome [3] 0 0
Biological Surrogate Markers
Timepoint [3] 0 0
At baseline and surgery
Secondary outcome [4] 0 0
Neurologic Symptoms
Timepoint [4] 0 0
At baseline
Secondary outcome [5] 0 0
Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure
Timepoint [5] 0 0
During and after surgery
Secondary outcome [6] 0 0
Image Defined Risk Factor (IDRF)
Timepoint [6] 0 0
At baseline

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

* Histologically confirmed neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/maturing subtype

* Newly diagnosed disease
* Intermediate-risk disease
* Needle biopsies or involved bone marrow are not sufficient for INPC histologic classification
* Meets 1 of the following criteria:

* Group 2

* International Neuroblastoma Staging System (INSS) stage 2A/2B; < 50% resected or biopsy only; = 12 years of age; MYCN-not amplified (NA); any histology and ploidy; normal 1p and 11q
* INSS stage 3; age < 365 days; MYCN-NA; favorable histology (FH); hyperdiploid (DI) > 1; normal 1p and 11q
* INSS stage 3; 365 days to 12 years of age; MYCN-NA; FH; normal 1p and 11q
* INSS stage 4S; age < 365 days; MYCN-NA; FH; DI >1; normal 1p and 11q; clinically symptomatic
* Group 3

* INSS stage 2A/2B; < 50% resected or biopsy only; = 12 years of age; MYCN-NA; any histology and ploidy; 1p loss of heterozygosity (LOH) and/or unb11q LOH (or data missing for either)
* INSS stage 3; age < 365 days; MYCN-NA; FH; DI > 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 3; age < 365 days; MYCN-NA; DI = 1 and/or unfavorable histology (UH); normal 1p and 11q
* INSS stage 3; 365 days to 12 years of age; MYCN-NA; FH; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4; age < 365 days; MYCN-NA; FH; DI > 1; normal 1p and 11q
* INSS stage 4S; age < 365 days; MYCN-NA; either UH and any ploidy or FH and DI = 1; normal 1p and 11q
* INSS stage 4S; age < 365 days; MYCN-NA; FH; DI > 1; 1p LOH and/or unb11q LOH (or data missing for either); clinically symptomatic
* Group 4

* INSS stage 3; age < 365 days; MYCN-NA; DI = 1 and/or UH; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 3; age 365 to < 547 days; MYCN-NA; UH; any ploidy; any 1p and 11q
* INSS stage 4, age < 365 days; MYCN-NA; DI = 1 and/or UH; any 1p and 11q
* INSS stage 4; age < 365 days; MYCN-NA; FH; DI > 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4; age 365 to < 547 days; MYCN-NA; FH; DI > 1; any 1p and 11q
* INSS stage 4S; age < 365 days; MYCN-NA; UH and any ploidy or FH and DI = 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4S; age < 365 days; unknown or incomplete biologic features

8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim.

Patients < 12 months of age with stg 3, 4, or 4S disease who achieve a very good PR (VGPR) to chemo (with the exception of resolution of skin or liver metastases in stage 4S patients) proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

* Must already be enrolled on protocol COG-ANBL00B1

* Simultaneous enrollment on COG-ANBL00B1 and this study allowed for clinical situations in which emergent treatment may be indicated including, but not limited to, the following criteria:

* 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 (e.g., abdominal compartment syndrome, urinary obstruction)
* Asymptomatic but, in the opinion of the treating physician, it is in the patient's best interest to begin chemotherapy immediately due to impending risk of neurologic impairment or organ dysfunction
* If patient receives study chemotherapy prior to undergoing diagnostic biopsy, the biopsy must be performed within 96 hours of beginning study therapy

* The only exception to this requirement is for patients with stage 4S disease who are considered too ill to undergo a diagnostic procedure will be waived the requirement for diagnostic tissue submission but will still need to be enrolled on COG-ANBL00B1

* For patients with stage 4S disease who are very ill and in whom an open biopsy to obtain tissue for diagnosis and biologic studies is considered medically contraindicated, every effort should be made to obtain some tumor tissue by either fine-needle aspiration of a metastatic site of disease and/or sampling of involved bone marrow, so that this tumor sample can be submitted for MYCN determination
* Patients who require emergent therapy, either prior to the diagnostic biopsy or before biology features are available, can be enrolled simultaneously on COG-ANBL00B1 and COG-ANBL0531 to receive emergent protocol therapy

* In emergent circumstances, COG-ANBL0531 protocol therapy may be initiated prior to enrollment on study as long as the patient has neuroblastoma by clinical diagnosis, all other COG-ANBL0531 eligibility criteria are met, and the COG-ANBL0531 Initial Therapy consent has been signed prior to starting protocol therapy; in this circumstance ANBL0531 enrollment must occur within 4 working days of starting protocol therapy
* Clinical situations in which emergent enrollment and treatment may be indicated include, but are not limited to, the following circumstances:

* 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 (e.g., abdominal compartment syndrome, urinary obstruction)
* Evolving hepatomegaly in infants less than 2 months of age

PATIENT CHARACTERISTICS:

* See Disease Characteristics

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No other prior chemotherapy or radiotherapy with the exception of dexamethasone
* No participation in another COG study with tumor therapeutic intent
Minimum age
No limit
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
6001 - Perth
Recruitment outside Australia
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Alabama
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Auckland
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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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clare Twist, MD
Address 0 0
Lucile Packard Children's Hospital at Stanford University Medical Center
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.