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

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

Status
Terminated
Phases
Early Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02212574
Enrollment
6
Registered
2014-08-08
Start date
2017-04-04
Completion date
2018-11-09
Last updated
2021-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Medulloblastoma

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

DRUGLomustine

Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1.

DRUGVincristine

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.

DRUGCisplatin

Chemotherapy Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.

DRUGCyclophosphamide

Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.

DRUGMesna

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

The Matthew Larson Foundation for Pediatric Brain Tumors
CollaboratorOTHER
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Progression Free Survival3 yearsTo 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

MeasureTime frameDescription
Patterns of Failure3 yearsTo 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

ArmCount
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
Total6

Baseline characteristics

CharacteristicChemotherapy
Age, Categorical
<=18 years
6 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
Age, Continuous7 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 typeEG000
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

Primary

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.

Secondary

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.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026