Clinical Trials /

Study Assessing the Feasibility of a Surgery and Chemotherapy-Only in Children With Wnt Positive Medulloblastoma

NCT02212574

Description:

Participants enrolling on this study will receive standard of care chemotherapy for Wnt positive medulloblastoma without the radiation therapy or the weekly chemotherapy that is given during radiation therapy.

Related Conditions:
  • Medulloblastoma
Recruiting Status:

Suspended

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Study Assessing the Feasibility of a Surgery and Chemotherapy-Only in Children With Wnt Positive Medulloblastoma
  • Official Title: Pilot Study Assessing the Feasibility of a Surgery and Chemotherapy-Only Approach in the Upfront Therapy of Children With Wnt Positive Standard Risk Medulloblastoma

Clinical Trial IDs

  • ORG STUDY ID: J1403
  • SECONDARY ID: NA_00091840
  • NCT ID: NCT02212574

Conditions

  • Medulloblastoma

Interventions

DrugSynonymsArms
LomustineCCNUChemotherapy
VincristineOncovinChemotherapy
CisplatinCisplatinumChemotherapy
CyclophosphamideCytoxanChemotherapy
MesnaMesnexChemotherapy
VincristineOncovinChemotherapy

Purpose

Participants enrolling on this study will receive standard of care chemotherapy for Wnt positive medulloblastoma without the radiation therapy or the weekly chemotherapy that is given during radiation therapy.

Detailed Description

      There will be 9 cycles of chemotherapy. There are two different kinds of cycles given. They
      are referred to as A and B.

      Cycle A lasts for 6 weeks and Cycle B lasts for 4 weeks. B cycles are given after the
      completion of two A cycles.

      Below are the details of the drugs and schedules for A and B cycles.

      Cycle A (This cycle lasts 42 days)

        -  Lomustine (CCNU) is given by mouth on Day 1.

        -  Vincristine is given directly into a vein (IV) over one minute or using a minibag over
           several minutes by some institutions on Days 1, 8, and 15.

        -  Cisplatin is given directly into a vein over 8 hours on Day 1

      Cycle B (This cycle lasts 28 days)

        -  Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.

        -  MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given
           15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours.

        -  Vincristine is given directly into a vein directly into the vein (IV) over one minute or
           using a minibag over several minutes by some institutions on Days 1 and 8.

      You may also get a supportive care drug called a myeloid growth factor (filgrastim or
      pegfilgrastim). This drug will help your blood counts recover after the chemotherapy is
      given.
    

Trial Arms

NameTypeDescriptionInterventions
ChemotherapyOtherChemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days. Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
  • Lomustine
  • Vincristine
  • Cisplatin
  • Cyclophosphamide
  • Mesna
  • Vincristine

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have classical histology posterior fossa medulloblastoma as
             determined by institutional neuro-pathological evaluation.

          -  Sufficient pathologic material must be available for central analysis and review

          -  Tumors will be deemed Wnt positive if, at the time of central analysis, there is:

          -  Monosomy 6 as determined by array CGH

          -  Gene transcript detection by NanoString supporting Wnt+ medulloblastoma

          -  Absence of large-cell, anaplastic histology

          -  Nuclear b-catenin IHC will be determined, but not required for the diagnosis

          -  Absence of residual or disseminated disease as defined by the following criteria:
             Minimal residual disease as determined by post-operative imaging preferably performed
             within 48 hours of resection (and at most 28 days post-surgery), i.e. gross total
             resection or residual disease of <1.5cm2 on post-operative imaging.

        No evidence of metastatic disease in the brain, spine or cerebral spinal fluid (CSF).
        Assessments must include MRI imaging of the brain and spine with and without contrast and a
        lumbar puncture for CSF cytology

          -  Diagnostic imaging (pre and post contrast) must be forwarded to Dana-Farber Cancer
             Institute (DFCI) for central review to confirm eligibility

          -  Patients must not have had any radiation therapy or chemotherapy for medulloblastoma
             prior to study enrollment

          -  Patients must have a Lansky performance status of >/=30 for children </=10 years of
             age or a Karnofsky performance status of > 30 for children > 10 years of age.

          -  Participants must have normal organ and marrow function as defined below:

          -  Hemoglobin greater than 10 g/dL (can be transfused). Hemoglobin <10 g/dL due to
             operative blood loss is permitted.

          -  Absolute neutrophil count > 1.0x109/L

          -  Platelets > 100,000/uL (non-transfused)

          -  Total bilirubin <1.5 x upper limit normal

          -  SGOT (AST) or SGPT (ALT) <2.5 x upper limit normal (ULN) for age

          -  Creatinine clearance or radioisotope GFR >70 ml/min/1.73m2 or normal serum creatinine
             for patient's age and gender

          -  All females of child-bearing age must have a negative pregnancy test before being
             enrolled on study. All patients of child-bearing age must practice an effective method
             of birth control whilst undergoing chemotherapy on study.

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to cisplatin, lomustine, vincristine or cyclophosphamide.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:3 years
Safety Issue:
Description:To determine the feasibility of treating newly diagnosed children with non-metastatic, standard risk, Wnt positive medulloblastoma with a chemotherapy-only approach. Primary outcome measure of this study will be progression-free survival.

Secondary Outcome Measures

Measure:Patterns of Failure
Time Frame:3 years
Safety Issue:
Description:To evaluate the patterns of failure in those children that do not have progressive disease, progression free survival and overall survival.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Wnt
  • Medulloblastoma
  • Chemotherapy

Last Updated

January 12, 2021