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High-Dose Iodine I 131 Metaiodobenzylguanidine, Topotecan, and Peripheral Stem Cell Transplant in Treating Young Patients With Relapsed Stage 4 Neuroblastoma or Primary Resistant High-Risk Neuroblastoma

Primary Purpose

Neuroblastoma

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
iodine I 131 metaiodobenzylguanidine
topotecan hydrochloride
chemotherapy
peripheral blood stem cell transplantation
radioisotope therapy
radionuclide imaging
radiosensitization
total-body irradiation
Sponsored by
Children's Cancer and Leukaemia Group
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma, localized resectable neuroblastoma, disseminated neuroblastoma

Eligibility Criteria

1 Year - 17 Years (Child)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of neuroblastoma meeting the 1 of the following criteria:

    • Primary resistant high-risk disease meeting the following criteria:

      • International neuroblastoma staging system (INSS) stage 4, or stage 2 or 3 with myelocytomatosis viral-related oncogene (MycN) amplification

      • Failed to achieve satisfactory remission with induction chemotherapy, defined as one of the following:

        • Less than 50% reduction or > 3 positive sites on iodine I 131 metaiodobenzylguanidine (^131I-MIBG) scintigraphy
        • Persistent cytomorphological positive disease in bone marrow aspirates or trephine biopsies
        • Progressive disease necessitating a change of treatment

    • Relapsed stage 4 disease meeting the following criteria:

      • High-risk neuroblastoma (INSS stage 4, or stage 2 or 3 with MycN amplification)

      • Relapsed after intensive treatment including high-dose chemotherapy and hematopoietic progenitor cell support

        • Patients may be entered at the time of relapse, or at any point subsequently after other treatments
  • ^131I-MIBG-positive disease on diagnostic scintigraphy
  • Peripheral blood stem cell harvest ≥ 300,000/mm³ CD 34+ cells
  • Enrolled in or has been treated on protocol SIOP-NB-2009 or a similar protocol

PATIENT CHARACTERISTICS:

  • Glomerular filtration rate ≥ 50 mL/min
  • Considered fit enough to undergo proposed study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Proportion of patients who respond to treatment (partial response and complete response at metastatic sites) as measured by metaiodobenzylguanidine scintigraphy and positron emission tomography and CT imaging
    Proportion of patients who are able to progress to potentially curative treatment with surgery and further systemic treatment
    Correlation of tumor dosimetry with response
    Time to tumor progression

    Secondary Outcome Measures

    Full Information

    First Posted
    October 18, 2006
    Last Updated
    July 9, 2013
    Sponsor
    Children's Cancer and Leukaemia Group
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00389766
    Brief Title
    High-Dose Iodine I 131 Metaiodobenzylguanidine, Topotecan, and Peripheral Stem Cell Transplant in Treating Young Patients With Relapsed Stage 4 Neuroblastoma or Primary Resistant High-Risk Neuroblastoma
    Official Title
    International Phase II Studies of I-mIBG in Combination With Topotecan and Peripheral Blood Stem Cell Rescue for (A) Primary Resistant High Risk Neuroblastoma and (B) Relapsed Stage 4 Neuroblastoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2007
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Withdrawn because protocol has been discontinued. It was never opened.
    Study Start Date
    July 2008 (undefined)
    Primary Completion Date
    July 2008 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Children's Cancer and Leukaemia Group

    4. Oversight

    5. Study Description

    Brief Summary
    RATIONALE: Radioisotope therapy, such as iodine I 131 metaiodobenzylguanidine (MIBG), releases radiation that kills tumor cells. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Topotecan may also make tumor cells more sensitive to iodine I 131 MIBG. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by iodine I 131 MIBG and topotecan. This may allow more iodine I 131 MIBG and topotecan to be given so that more tumor cells are killed. PURPOSE: This phase II trial is studying how well giving high-dose iodine I 131 MIBG together with topotecan and peripheral stem cell transplant works in treating young patients with relapsed stage 4 neuroblastoma or primary resistant high-risk neuroblastoma.
    Detailed Description
    OBJECTIVES: Determine response (partial and complete response at metastatic sites) in children with relapsed stage 4 neuroblastoma or primary resistant high-risk neuroblastoma treated with high-dose iodine I 131 metaiodobenzylguanidine, topotecan hydrochloride, and peripheral blood stem cell transplantation. Determine the proportion of patients who, as a result of this treatment, are able to progress to potentially curative surgery and further systemic treatment. Correlate tumor dosimetry (to determine whether the tumor absorbed the radiation dose) with response in patients treated with this regimen. Determine the time to tumor progression. OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease type (relapsed stage 4 vs primary resistant high-risk neuroblastoma). Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 and 15-19 and high-dose iodine I 131 metaiodobenzylguanidine (^131I-MIBG) IV over 30 minutes on days 1 and 15. Patients receive autologous CD 34+ peripheral blood stem cells when ^131I-MIBG dosimetry levels reach an acceptable low on days 25-29. Total whole-body absorbed dose is measured periodically after the first ^131I-MIBG dose is administered and periodically thereafter. After completion of study treatment, patients are followed periodically for up to 10 years. PROJECTED ACCRUAL: A total of 67 patients will be accrued for this study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neuroblastoma
    Keywords
    localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma, localized resectable neuroblastoma, disseminated neuroblastoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Masking
    None (Open Label)
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    iodine I 131 metaiodobenzylguanidine
    Intervention Type
    Drug
    Intervention Name(s)
    topotecan hydrochloride
    Intervention Type
    Procedure
    Intervention Name(s)
    chemotherapy
    Intervention Type
    Procedure
    Intervention Name(s)
    peripheral blood stem cell transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    radioisotope therapy
    Intervention Type
    Procedure
    Intervention Name(s)
    radionuclide imaging
    Intervention Type
    Procedure
    Intervention Name(s)
    radiosensitization
    Intervention Type
    Procedure
    Intervention Name(s)
    total-body irradiation
    Primary Outcome Measure Information:
    Title
    Proportion of patients who respond to treatment (partial response and complete response at metastatic sites) as measured by metaiodobenzylguanidine scintigraphy and positron emission tomography and CT imaging
    Title
    Proportion of patients who are able to progress to potentially curative treatment with surgery and further systemic treatment
    Title
    Correlation of tumor dosimetry with response
    Title
    Time to tumor progression

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Confirmed diagnosis of neuroblastoma meeting the 1 of the following criteria: Primary resistant high-risk disease meeting the following criteria: International neuroblastoma staging system (INSS) stage 4, or stage 2 or 3 with myelocytomatosis viral-related oncogene (MycN) amplification Failed to achieve satisfactory remission with induction chemotherapy, defined as one of the following: Less than 50% reduction or > 3 positive sites on iodine I 131 metaiodobenzylguanidine (^131I-MIBG) scintigraphy Persistent cytomorphological positive disease in bone marrow aspirates or trephine biopsies Progressive disease necessitating a change of treatment Relapsed stage 4 disease meeting the following criteria: High-risk neuroblastoma (INSS stage 4, or stage 2 or 3 with MycN amplification) Relapsed after intensive treatment including high-dose chemotherapy and hematopoietic progenitor cell support Patients may be entered at the time of relapse, or at any point subsequently after other treatments ^131I-MIBG-positive disease on diagnostic scintigraphy Peripheral blood stem cell harvest ≥ 300,000/mm³ CD 34+ cells Enrolled in or has been treated on protocol SIOP-NB-2009 or a similar protocol PATIENT CHARACTERISTICS: Glomerular filtration rate ≥ 50 mL/min Considered fit enough to undergo proposed study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mark N. Gaze, MD
    Organizational Affiliation
    University College London Hospitals
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    High-Dose Iodine I 131 Metaiodobenzylguanidine, Topotecan, and Peripheral Stem Cell Transplant in Treating Young Patients With Relapsed Stage 4 Neuroblastoma or Primary Resistant High-Risk Neuroblastoma

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