AzTrials
AzTrials

NeuroblastomaPhase 3NCT00499616

Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma

A Phase 3 study testing carboplatin, cyclophosphamide and doxorubicin hydrochloride in people with Neuroblastoma, run by Children's Oncology Group at 189 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages Up to 12 years
Conditions the study is for
Neuroblastoma
What is being tested?
carboplatin, cyclophosphamide and doxorubicin hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
464 participants
Where
189 sitesin 6 countries
Study dates
8 Oct 2007to 30 Jun 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 12 years
  • All sexes
  • No healthy volunteers
  • Child

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

Trial locations and contacts

189 sites in 6 countries.

189 sites in 6 countries

United States166 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308-1062

  • Albany Medical Center Hospital

    Albany, New York, 12208-3419

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87131-5636

  • Tulane Cancer Center Office of Clinical Research

    Alexandria, Louisiana, 71315-3198

  • Texas Tech University Health Sciences Center School of Medicine - Amarillo

    Amarillo, Texas, 79106

  • C.S. Mott Children's Hospital at University of Michigan Medical Center

    Ann Arbor, Michigan, 48109-0286

  • Mission Hospitals - Memorial Campus

    Asheville, North Carolina, 28801

  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

    Atlanta, Georgia, 30322

  • MBCCOP - Medical College of Georgia Cancer Center

    Augusta, Georgia, 30912-3730

  • Children's Hospital Center for Cancer and Blood Disorders

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Baltimore, Maryland, 21215

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • CancerCare of Maine at Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Mountain States Tumor Institute at St. Luke's Regional Medical Center

    Boise, Idaho, 83712-6297

  • Floating Hospital for Children at Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Maimonides Cancer Center at Maimonides Medical Center

    Brooklyn, New York, 11219

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Fletcher Allen Health Care - University Health Center Campus

    Burlington, Vermont, 05401

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Health Sciences Center - Charleston

    Charleston, West Virginia, 25302

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Presbyterian Cancer Center at Presbyterian Hospital

    Charlotte, North Carolina, 28233-3549

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • T.C. Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Geisinger Cancer Institute at Geisinger Health

    Danville, Pennsylvania, 17822-0001

  • Dayton Children's - Dayton

    Dayton, Ohio, 45404-1815

  • Presbyterian - St. Luke's Medical Center

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Southern California Permanente Medical Group

    Downey, California, 90027

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042-3300

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Broward General Medical Center Cancer Center

    Fort Lauderdale, Florida, 33316

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Greenville Hospital Cancer Center

    Greenville, South Carolina, 29605

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033-0850

  • Memorial Cancer Institute at Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 96813

  • Baylor University Medical Center - Houston

    Houston, Texas, 77030-2399

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • CCOP - Kalamazoo

    Kalamazoo, Michigan, 49007-5381

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37901

  • Breslin Cancer Center at Ingham Regional Medical Center

    Lansing, Michigan, 48910

  • CCOP - Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89109-2306

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

    Long Beach, California, 90801

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Children's Hospital Central California

    Madera, California, 93638-8762

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • Cardinal Bernardin Cancer Center at Loyola University Medical Center

    Maywood, Illinois, 60153

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Baptist-South Miami Regional Cancer Program

    Miami, Florida, 33176

  • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • University of South Alabama Mitchell Cancer Institute

    Mobile, Alabama, 36604

  • Overlook Hospital

    Morristown, New Jersey, 07962

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • Yale Cancer Center

    New Haven, Connecticut, 06520-8028

  • Schneider Children's Hospital

    New Hyde Park, New York, 11040

  • NYU Cancer Institute at New York University Medical Center

    New York, New York, 10016

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507-1971

  • Keyser Family Cancer Center at Advocate Hope Children's Hospital

    Oak Lawn, Illinois, 60453

  • Children's Hospital and Research Center Oakland

    Oakland, California, 94609

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital

    Omaha, Nebraska, 68114-4113

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-6805

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Florida Hospital Cancer Institute at Florida Hospital Orlando

    Orlando, Florida, 32803-1273

  • M.D. Anderson Cancer Center at Orlando

    Orlando, Florida, 32806

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital at Stanford University Medical Center

    Palo Alto, California, 95798

  • Advocate Lutheran General Cancer Care Center

    Park Ridge, Illinois, 60068-1174

  • St. Joseph's Hospital and Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134-1095

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15213

  • Legacy Emanuel Hospital and Health Center and Children's Hospital

    Portland, Oregon, 97227

  • Knight Cancer Institute at Oregon Health and Science University

    Portland, Oregon, 97239-3098

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708-2197

  • Rhode Island Hospital Comprehensive Cancer Center

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • Carilion Medical Center for Children at Roanoke Community Hospital

    Roanoke, Virginia, 24014

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Sutter Cancer Center

    Sacramento, California, 95816

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • Kaiser Permanente Medical Center - Oakland

    Sacramento, California, 95825

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123-4282

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

    Savannah, Georgia, 31403-3089

  • Maine Children's Cancer Program at Barbara Bush Children's Hospital

    Scarborough, Maine, 04074-9308

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Sanford Cancer Center at Sanford USD Medical Center

    Sioux Falls, South Dakota, 57117-5039

  • Providence Cancer Center at Sacred Heart Medical Center

    Spokane, Washington, 99220-2555

  • Simmons Cooper Cancer Institute

    Springfield, Illinois, 62794-9677

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center - Tacoma

    Tacoma, Washington, 98405

  • Madigan Army Medical Center - Tacoma

    Tacoma, Washington, 98431

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Albert Einstein Cancer Center at Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Toledo Hospital

    Toledo, Ohio, 43606

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • Tripler Army Medical Center

    Tripler AMC, Hawaii, 96859-5000

  • Arizona Cancer Center at University of Arizona Health Sciences Center

    Tucson, Arizona, 85724-5024

  • New York Medical College

    Valhalla, New York, 10595

  • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Walter Reed Army Medical Center

    Washington D.C., District of Columbia, 20307-5001

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

Other trials in United States

Canada15 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 1Z2

  • IWK Health Centre

    Halifax, Nova Scotia, B3J 3G9

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 2V7

  • Children's Hospital of Western Ontario

    London, Ontario, N6A 5W9

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

  • Allan Blair Cancer Centre at Pasqua Hospital

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

  • Janeway Children's Health and Rehabilitation Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia4 sites

  • Royal Children's Hospital

    Brisbane, Queensland, 4029

  • Women's and Children's Hospital

    North Adelaide, South Australia, 5006

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

  • Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

New Zealand2 sites

  • Starship Children's Health

    Auckland, 1

  • Christchurch Hospital

    Christchurch, 8140

Other trials in New Zealand

Netherlands1 site

  • Universitair Medisch Centrum St. Radboud - Nijmegen

    Nijmegen, 6500

Other trials in Netherlands

Puerto Rico1 site

  • San Jorge Children's Hospital

    Santurce, 00912

Other trials in Puerto Rico

About this study

Official title: Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma

RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Isotretinoin may help neuroblastoma cells become more like normal cells, and grow and spread more slowly. Giving combination chemotherapy before surgery may make the tumor smaller and make it more likely that the tumor can be surgically removed. It is not yet known what is the minimal amount of chemotherapy needed to achieve sufficient tumor shrinkage to control intermediate risk neuroblastoma and prevent tumor recurrence or metastases.

PURPOSE: This phase III trial is designed to reduce therapy for patients with favorable biology intermediate risk neuroblastoma by decreasing the number of chemotherapy cycles administered and by allowing for up to 50% residual tumor volume for patients with localized disease.

Read the detailed description

OBJECTIVES:

Primary

  • Reduce therapy for patients with intermediate-risk neuroblastoma while maintaining a 3-year overall survival (OS) rate of ≥ 95% by using a response-based duration of therapy algorithm.
  • Maintain an overall 3-year OS rate of ≥ 90% for patients within each group.
  • Utilize loss of heterozygosity, prospectively, at 1p36 and 11q23 to refine risk-stratification and treatment assignment, allowing patients whose tumors lack these chromosomal abnormalities to receive a reduction in therapy, and compare the outcome with patients treated on COG-A3961.
  • Reduce intensity of therapy for patients 365 to < 547 days (12-18 months) of age with stage 4 neuroblastoma and favorable biological features and maintain a 3-year event-free survival (EFS) rate consistent with that for patients < 1 year of age with stage 4 neuroblastoma treated on COG-A3961.
  • Reduce intensity of therapy for patients 365 to < 547 days (12-18 months) of age with stage 3 MYCN-nonamplified but unfavorable histology neuroblastoma and maintain a 3-year EFS rate consistent with that for patients < 1 year of age with stage 3, MYCN-nonamplified, unfavorable histology neuroblastoma treated on COG-A3961.
  • Reduce surgical morbidity for patients with stage 4S neuroblastoma by allowing for biopsy only, rather than complete surgical resection, of the primary tumor.
  • Systematically study the outcome of patients with stage 4S neuroblastoma who are unable to undergo biopsy for biology-based risk assignment.
  • Determine if the extent of surgical resection correlates with the maintenance of local control, EFS and/or OS rates, and surgical complication rate.

Secondary

  • Determine the results of a standard retrieval approach for patients with residual disease after 8 courses of initial therapy.
  • Determine the results of a standard retrieval approach for patients with progressive, nonmetastatic disease.
  • Identify additional biological surrogate markers for disease relapse and/or metastatic progression.
  • Describe the neurologic outcome of patients with paraspinal neuroblastoma primary tumors.
  • Correlate surgical biopsy technique with adequacy of tissue acquisition for biologic studies and with complications associated with the biopsy procedure.
  • Prospectively validate the prognostic ability of the International Neuroblastoma Risk Group image-defined risk factor system, and compare the institutional assessment of image-defined risk factors with that of central review.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 3 treatment groups by risk-stratification based on age, stage (INSS stage 2, 3, 4, or 4S), MYCN status (amplified vs not amplified), histopathologic classification, tumor DNA index, and allelic status at chromosome bands 11q23 and 1p36.

  • Initial chemotherapy: Courses of initial chemotherapy are administered every 21 days according to group assignment as outlined below:
  • Course 1: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
  • Course 2: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour, and doxorubicin hydrochloride IV over 15 minutes on day 1.
  • Course 3: Patients receive cyclophosphamide IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
  • Course 4: Patients receive carboplatin IV over 1 hour and doxorubicin hydrochloride IV over 15 minutes on day 1 and etoposide IV over 1 hour on days 1-3.
  • Course 5: Patients receive cyclophosphamide IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
  • Course 6: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour, and doxorubicin hydrochloride IV over 15 minutes on day 1.
  • Course 7: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
  • Course 8: Patients receive cyclophosphamide IV over 1 hour and doxorubicin hydrochloride IV over 15 minutes on day 1.
  • Group 2: Patients receive 2 courses of initial chemotherapy. Patients with a partial response (PR) (50-90% reduction in volume) to chemotherapy proceed to observation. Patients without a PR receive 2-6 additional courses of chemotherapy (beginning with course 3). Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy.
  • Group 3: Patients receive 4 courses of initial chemotherapy. Patients with a PR after chemotherapy proceed to observation. Patients without a PR receive 2-4 additional courses of chemotherapy (beginning with course 5). Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy.
  • Group 4: Patients receive 8 courses of initial chemotherapy. Patients under 12 months of age with stage 3, 4, or 4S disease who achieve a very good PR (VGPR) (> 90% reduction in the volume of the primary tumor and resolution of metastatic disease, with the exception of liver and skin metastases) to chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease [age 365 to < 547 days at diagnosis, INSS stage 3, MYCN-NA, unfavorable histology, any ploidy and patients age 365 to < 547 days at diagnosis, INSS stage 4, MYCN-NA, favorable histology, DI > 1] who achieve a VGPR proceed to isotretinoin therapy. Patients who do not achieve a VGPR after 8 courses of initial chemotherapy +/- surgery will proceed to retrieval chemotherapy with cyclophosphamide/topotecan for 2-6 courses until a VGPR can be achieved with a combination of chemotherapy and surgery.
  • Retrieval chemotherapy*: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 6 courses.
  • Groups 2 and 3: Patients with a PR after 2-6 courses of retrieval chemotherapy proceed to observation. Patients without a PR after 2-6 courses of retrieval chemotherapy are removed from protocol therapy.
  • Group 4: Patients under 12 months of age with stage 4 disease with a VGPR after retrieval chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease who achieve a VGPR after retrieval chemotherapy proceed to isotretinoin therapy. Patients who do not achieve a VGPR after retrieval chemotherapy are removed from protocol therapy.

Group 4 patients who develop progressive, non-metastatic disease within 3 years of study enrollment will also receive retrieval chemotherapy with cyclophosphamide and topotecan.

NOTE: *Patients who have previously received cyclophosphamide and topotecan to achieve first PR/VGPR are not eligible for this Retrieval Therapy.

  • 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. Reassessment for definitive surgery (for patients who undergo biopsy only or partial resection at diagnosis) is made at the completion of scheduled chemotherapy (after course 2 for group 2, after course 4 for group 3, and after course 8 for group 4).
  • Isotretinoin therapy: Beginning 3-4 weeks after completion of chemotherapy or 2 weeks post-operatively (for patients who undergo surgical resection), patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up periodically for up to 10 years.

Conditions
Neuroblastoma
Being tested
carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, topotecan hydrochloride
Keywords
regional neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, localized unresectable neuroblastoma, localized resectable neuroblastoma
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • carboplatinDrug

    Also called Paraplatin, NSC #241240

    Given IV

  • cyclophosphamideDrug

    Also called Cytoxan, NSC #26271

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called Adriamycin, NSC #123127

    Given IV

  • etoposideDrug

    Also called VePesid, VP-16, NSC #141540

    Given orally

  • topotecan hydrochlorideDrug

    Also called SKF-104864, Hycamtin, NSC #60969

    Given IV

  • IsotretinoinDrug

    Also called 13-cis-retinoic acid, RO-43, 780, Accutane

    Given orally

  • SurgeryProcedure or 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.

  • FilgrastimDrug

    Also called Granulocyte Colony-Stimulating Factor, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629

    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.

Study groups in NCT00499616
Study groupRoleWhat they receive
Group 2 (chemotherapy, surgery)Experimental2 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.
Receives: Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: topotecan hydrochloride; Procedure: Surgery; Drug: Filgrastim
Group 3 (chemotherapy, surgery)Experimental4 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.
Receives: Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: topotecan hydrochloride; Procedure: Surgery; Drug: Filgrastim
Group 4 (chemotherapy, surgery, antineoplastic therapy)Experimental8 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.
Receives: Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: topotecan hydrochloride; Drug: Isotretinoin; Procedure: Surgery; Drug: Filgrastim
Non-intermediate risk enrolled on intermediate risk trialExperimentalThe 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.
Receives: Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS) Rates

    OS time is calculated from date of enrollment until death, or until last contact if the patient is alive.

    Measured: 3 years

  2. Definitive Determination of the Prognostic Ability of 1p and 11q

    Addressed by a descriptive comparison of the EFS and OS rates for patients with 1p loss vs without 1p loss, and for those with unbalanced 11q vs normal 11q.

    Measured: At baseline

  3. 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

    Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age.

    Measured: Up to 3 years

  4. Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961

    Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age

    Measured: Up to 3 years

  5. Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma

    Descriptive analyses of the proportion of stage 4S infants that experience a surgical or post-operative event.

    Measured: Up to 3 years

  6. Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment

    Kaplan-Meier curves and lifetables of Event Free Survival (EFS) and Overall Survival (OS) rates will be generated to describe the outcome of the stage 4S infants unable to undergo biopsy.

    Measured: From baseline to up to 10 years

  7. Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)

    To test the predictive ability of the extent of surgical resection for EFS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.

    Measured: Up to 10 years

  8. Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates

    To test the predictive ability of the extent of surgical resection for OS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.

    Measured: Up to 10 years

  9. Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate

    To test for the association of the extent of surgical resection (CR vs <CR) with surgical complications rate (complications of any kind vs no complications at all), a chi-square test will be performed.

    Measured: Up to 10 years

Secondary outcomes (6)

  1. Second-event-free Survival (E2FS)

    E2FS (from time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.

    Measured: 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

  2. Second-Overall Survival

    OS (from the time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.

    Measured: From the time of the first progressive, non-metastatic event; up to 3 years

  3. Biological Surrogate Markers

    Multivariable analyses will be performed to identify variables of prognostic interest.

    Measured: At baseline and surgery

  4. Neurologic Symptoms

    Percentage of patients with neurologic symptoms will be calculated. Includes patients with paraspinal or intraspinal tumors, including epidural tumors with or without spinal cord compression. Neurologic symptoms include back or extremities neurologic symptoms, motor deficit, abnormal sensation, abnormal bladder/bowel sphincteric function, chronic pain in back or extremities, scoliosis, kyphosis, or clinically relevant/functional abnormality in size or contour of leg or foot.

    Measured: At baseline

  5. Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure

    A chi-square test will be performed.

    Measured: During and after surgery

  6. Image Defined Risk Factor (IDRF)

    Percentage of patients with presence of one or more IDRFs will be calculated. IDRFs describe anatomic features which may make surgical resection more difficult.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2007 (estimated)
  2. Study start8 Oct 2007
  3. Primary completion30 Jun 2014
  4. Study completion30 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
464 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00499616
Sponsor's protocol ID
ANBL0531
Other IDs
COG-ANBL0531, NCI-2009-00400
Status last verified
Jun 2021
First submitted
10 Jul 2007
Last updated
6 Jul 2021
Data monitoring committee
Yes

Publications

  • Twist CJ, Schmidt ML, Naranjo A, London WB, Tenney SC, Marachelian A, Shimada H, Collins MH, Esiashvili N, Adkins ES, Mattei P, Handler M, Katzenstein H, Attiyeh E, Hogarty MD, Gastier-Foster J, Wagner E, Matthay KK, Park JR, Maris JM, Cohn SL. Maintaining Outstanding Outcomes Using Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531. J Clin Oncol. 2019 Dec 1;37(34):3243-3255. doi: 10.1200/JCO.19.00919. Epub 2019 Aug 6.

    PubMed 31386611

  • Twist CJ, Naranjo A, Schmidt ML, Tenney SC, Cohn SL, Meany HJ, Mattei P, Adkins ES, Shimada H, London WB, Park JR, Matthay KK, Maris JM. Defining Risk Factors for Chemotherapeutic Intervention in Infants With Stage 4S Neuroblastoma: A Report From Children's Oncology Group Study ANBL0531. J Clin Oncol. 2019 Jan 10;37(2):115-124. doi: 10.1200/JCO.18.00419. Epub 2018 Nov 16.

    PubMed 30444686

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing carboplatin, cyclophosphamide and doxorubicin hydrochloride in people with Neuroblastoma, run by Children's Oncology Group at 189 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 189 sites in United States, Canada, Australia, New Zealand, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) Rates (time frame: 3 years). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00499616, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2021.

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