Text Size

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00499616
First received: July 10, 2007
Last updated: August 3, 2012
Last verified: July 2011
History of Changes
  Purpose

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 with or without isotretinoin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which treatment regimen is more effective in treating young patients with neuroblastoma.

PURPOSE: This phase III trial is comparing different regimens of combination chemotherapy and surgery with or without isotretinoin to see how well they work in treating young patients with neuroblastoma.


Condition Intervention Phase
Neuroblastoma
 Drug: carboplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: topotecan hydrochloride
 Phase 3

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Neuroblastoma
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 464
Study Start Date: October 2007
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Patients receive 2 courses of initial chemotherapy. Patients with a partial response (PR) 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 comprising cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
 Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: topotecan hydrochloride
Given IV
Experimental: Group 2
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 as in group 1. Some patients may also undergo surgery.
 Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: topotecan hydrochloride
Given IV
Experimental: Group 3
Patients receive 8 courses of initial chemotherapy. Patients under 12 months of age with stage 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease who achieve a VGPR proceed to isotretinoin therapy. Patients who do not achieve a VGPR proceed to retrieval chemotherapy as in group 1. Some patients may also undergo surgery.
 Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: topotecan hydrochloride
Given IV
Experimental: Group 4
Patients receive 8 courses of initial chemotherapy. If a VGPR cannot be achieved following 8 courses of first-line chemotherapy +/- surgery, or progressive, non-metastatic disease develops within 3 years of study enrollment, then patients receive retrieval chemotherapy as in group 1 until VGPR can be achieved. Some patients may also undergo surgery and then proceed to isotretinoin therapy.
 Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: etoposide
Given IV
Drug: topotecan hydrochloride
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 1

      • 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); hyperdyploid (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 2

      • 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 3

      • 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

    • Group 4

      • INSS stage 3, age < 365 days, MYCN-NA, either 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 3
      • INSS stage 4, age < 365 days, MYCN-NA either 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, either UH and any ploidy or FH and DI = 1 and 1p LOH and/or unb11q LOH (or data missing for either)
      • INSS stage 4S, age < 365 days, unknown MYCN, histology, and/or ploidy

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00499616

  Show 189 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Clare Twist, MD Lucile Packard Children's Hospital at Stanford University Medical Center
Investigator: Mary Lou Schmidt, MD University of Illinois
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT00499616     History of Changes
Other Study ID Numbers: CDR0000554708, COG-ANBL0531
Study First Received: July 10, 2007
Last Updated: August 3, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
localized resectable neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Doxorubicin
Etoposide
Carboplatin
Topotecan
 Isotretinoin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Phytogenic
Dermatologic Agents

ClinicalTrials.gov processed this record on May 19, 2013