Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin

This study is currently recruiting participants.
Verified April 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01175356
First received: August 3, 2010
Last updated: April 6, 2012
Last verified: April 2012
  Purpose

RATIONALE: Radioisotope therapy, such as iobenguane I 131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that are destroyed by iobenguane I 131 and chemotherapy.

PURPOSE: This clinical trial is studying induction therapy followed by iobenguane I 131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin.


Condition Intervention
Neuroblastoma
Drug: busulfan
Drug: cisplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: irinotecan hydrochloride
Drug: isotretinoin
Drug: melphalan
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Other: pharmacological study
Other: questionnaire administration
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: external beam radiation therapy
Radiation: intensity-modulated radiation therapy
Radiation: iobenguane I 131

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A COG Pilot Study of Intensive Induction Therapy and 131I-MIBG With Myeloablative Carboplatin, Etoposide and Melphalan (CEM) for Newly Diagnosed High-Risk Neuroblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Proportion of patients treated with iodine I 131 meta-iodobenzylguanidine (131 I-MIBG), carboplatin, etoposide phosphate, and melphalan [ Designated as safety issue: No ]
  • 1-year event-free survival rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Tumor burden [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Relationship of sinusoidal obstruction syndrome to dosages of myeloablative consolidation therapy and autologous stem cell rescue, and whole-body radiation dose or delay of radiation clearance due to 131 I-MIBG [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: December 2011
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites meeting 1 of the following staging criteria:

    • Newly diagnosed International Neuroblastoma Staging System (INSS) stage 4 disease meeting 1 of the following criteria:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days regardless of additional biologic features
      • Age > 18 months (> 547 days) regardless of biologic features
      • Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features: MYCN amplification, unfavorable pathology, and/or DNA index = 1, or any biologic feature that is indeterminant, unsatisfactory, or unknown
    • Newly diagnosed INSS stage 3 disease meeting 1 of the following criteria:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days, regardless of additional biologic features
      • Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
    • Newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days, regardless of additional biologic features
    • Age ≥ 365 days initially diagnosed with INSS stage 1, 2, or 4S who progressed (within the past 4 weeks) to a stage 4 without interval chemotherapy
    • No patients aged 12-18 months with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1)
  • Must be enrolled onto ANBL00B1 biologic study
  • Must have ≥ 1 "MIBG-avid target lesion" present on MIBG scan in the past 4 weeks

PATIENT CHARACTERISTICS:

  • Total bilirubin ≤1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 10 times ULN
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

    • ≤ 0.6 mg/dL (1 to < 2 years of age)
    • ≤ 0.8 mg/dL (2 to < 6 years of age)
    • ≤ 1.0 mg/dL (6 to < 10 years of age)
    • ≤ 1.2 mg/dL (10 to < 13 years of age)
    • ≤ 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • ≤ 1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by radionuclide evaluation
  • Able to tolerate peripheral blood stem cell (PBSC) collection

    • No contraindications to PBSC collection including weight, size, or physical condition that would preclude apheresis

PRIOR CONCURRENT THERAPY:

  • No prior systemic therapy

    • Localized emergency radiotherapy to sites of life-threatening or function-threatening disease and ≥ 1 measurable lesion is not irradiated
    • No more than 1 course of chemotherapy per low- or intermediate-risk neuroblastoma therapy before determination of MYCN amplification and histology
  • No local radiotherapy that includes any of the following:

    • 1,200 cGy to more than 33% of both kidneys

      • Patient must have ≥ 1 kidney that has not exceeded the dose/volume of radiation listed
    • 1,800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver
  • No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175356

Locations
United States, Alabama
UAB Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - UAB Comprehensive Cancer Center     205-934-0309        
United States, California
Childrens Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Leo Mascarenhas     323-361-2529        
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, Colorado
Children's Hospital Colorado Center for Cancer and Blood Disorders Recruiting
Aurora, Colorado, United States, 80045
Contact: Kelly W. Maloney     720-777-6673        
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Clinical Trials Office - Children's National Medical Center     202-884-2549        
United States, Illinois
University of Chicago Cancer Research Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Clinical Trials Office - University of Chicago Cancer Research     773-834-7424        
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica     513-636-2799        
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Elizabeth Fox     267-425-3010        
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Brian Weiss, MD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT01175356     History of Changes
Other Study ID Numbers: CDR0000682629, COG-ANBL09P1
Study First Received: August 3, 2010
Last Updated: April 6, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
disseminated neuroblastoma
localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma
stage 4S 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
Busulfan
Cyclophosphamide
Melphalan
Etoposide phosphate
Irinotecan
Cisplatin
Doxorubicin
Etoposide
Vincristine
3-Iodobenzylguanidine
Camptothecin
Topotecan
Isotretinoin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013