Medulloblastoma
Conditions
Keywords
Wnt, Medulloblastoma, Chemotherapy
Brief summary
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.
Interventions
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1.
Chemotherapy Cycle A 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.
Chemotherapy Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.
Chemotherapy Cycle B 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.
Sponsors
Study design
Eligibility
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 3 years | 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; the number of participants who with progression free survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patterns of Failure | 3 years | To evaluate the patterns of failure in those children that do not have progressive disease, progression free survival and overall survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Chemo Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days.
Chemo Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide, repeated at 3 and 6 hours. Vincristine 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 & 8. Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine: Chemo Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15.
Cisplatin: Chemo Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.
Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 2.
Mesna: Chemo Cycle B MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide, repeated at 3 & 6 hours.
Vincristine: Chemo Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Chemotherapy |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Progression Free Survival
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; the number of participants who with progression free survival.
Time frame: 3 years
Population: This outcome was not assessed because some patients had a relapse and study was abruptly terminated.
Patterns of Failure
To evaluate the patterns of failure in those children that do not have progressive disease, progression free survival and overall survival.
Time frame: 3 years
Population: This outcome was not assessed because some patients had a relapse and study was abruptly terminated.