Pilot Study Assessing the Feasibility of a Surgery and Chemotherapy-Only Approach in the Upfront Therapy of Children with Wnt Positive Standard Risk Medulloblastoma
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.
Ages Eligible for Study: 3 Years to 18 Years Genders Eligible for Study: Both Accepts Healthy Volunteers: No •Participants must have classical histology posterior fossa medulloblastoma as determined by institutional neuro-pathological evaluation.•Institutional beta- catenin staining must demonstrate nuclear reactivity by immunohistochemistry•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:•Confirmation of beta-catenin nuclear reactivity by immunohistochemistry.•Monosomy 6 as determined by array CGH•Absence of MYCN or MYC amplification (as determined by FISH)•Absence of large-cell, anaplastic histology•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 less than 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•Patients must not have had any radiation therapy or chemotherapy for medulloblastoma prior to study enrollment•Patients must have a Lansky performance status of greater than / equal to 30 for children less than / equal to 10 years of age or a Karnofsky performance status of greater than 30 for children greater than 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 less than 10 g/dL due to operative blood loss is permitted.•Absolute neutrophil count greater than 1.0x109/L•Platelets greater than 100,000/uL (non-transfused)•Total bilirubin less than 1.5 x upper limit normal•SGOT (AST) or SGPT (ALT) less than 2.5 x upper limit normal (ULN) for age•Creatinine clearance or radioisotope GFR greater than 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.
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 1Cycle 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.
09/19/2014 04:03 AM