Official Title
A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients
Summary:
This phase II trial studies how well reduced doses of radiation therapy to the brain and
spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of
brain tumour called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using
chemotherapy and radiation therapy have been shown to be effective in treating patients with
WNT-driven medulloblastoma. However, there is a concern about the late side effects of
treatment, such as learning difficulties, lower amounts of hormones, or other problems in
performing daily activities. Radiation Therapy uses high-energy radiation from x-rays to kill
cancer cells and shrink tumours. Drugs used in chemotherapy, such as cisplatin, vincristine
sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumour
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumour
cells and may also reduce the late side effects of treatment.
Trial Description
Primary Outcome:
- Progression-free survival (PFS)
Secondary Outcome:
- Deoxyribonucleic acid (DNA) methylation profiling as real-time classification of WNT-driven medulloblastoma
- Change in neurocognitive function (cognitive, social, emotional and behavioural) according to Children Oncology Group Standard Neuropsychological Battery
PRIMARY OBJECTIVE:
I. To estimate the progression-free survival (PFS) of children >= 3 years of age with
wingless-type MMTV integration site family (WNT)-driven average-risk medulloblastoma using
reduced craniospinal radiation therapy (CSI) (18 Gray [Gy]) with a limited target volume boost to
the tumour bed of 36 Gy for a total of 54 Gy and reduced chemotherapy approach (no vincristine
[vincristine sulfate] during radiation therapy and reduced-dose maintenance chemotherapy) and to
monitor the PFS for early evidence that the outcome is unacceptable.
SECONDARY OBJECTIVES:
I. To prospectively test the hypothesis that deoxyribonucleic acid (DNA) methylation
profiling will accurately classify WNT-driven medulloblastoma.
II. To prospectively evaluate and longitudinally model the cognitive, social, emotional,
behavioural, and quality of life (QoL) functioning of children who are treated with reduced
CSI (18 Gy) with a limited target volume boost to the tumour bed (to a total of 54 Gy) and
reduced chemotherapy (reduced cisplatin, vincristine, and lomustine [CCNU]).
EXPLORATORY OBJECTIVES:
I. To explore whether DNA methylation profiling of medulloblastoma samples will result in a
predictive classification scheme for the Sonic Hedgehog (SHH), Group 3, and Group 4
medulloblastoma subgroups according to the Heidelberg classifier. This will be addressed in a
separate biology protocol.
II. To describe the audiologic and endocrinologic toxicities, as well as peripheral
neuropathy, in children treated with reduced CSI (18 Gy) with a limited target volume boost
to the tumour bed (to a total of 54 Gy) and reduced cisplatin and vincristine chemotherapy.
OUTLINE:
RADIATION THERAPY: Beginning 4-5 weeks after surgery, patients undergo craniospinal radiation
therapy 5 days a week for 6 weeks.
MAINTENANCE THERAPY (WEEKS 1, 3, 5, and 7): Beginning 4-6 weeks after completion of radiation
therapy patients receive lomustine orally (PO) on day 1, vincristine sulfate intravenously
(IV) over 1 minute or via minibag on days 1, 8, and 15, and cisplatin IV over 6 hours on day
1. Treatment repeats every 42 days in the absence of disease progression or unacceptable
toxicity.
MAINTENANCE THERAPY (WEEKS 2, 4, AND 6): Patients receive cyclophosphamide IV over 30-60
minutes on days 1 and 2, mesna IV over 15-30 minutes on days 1 and 2, and vincristine sulfate
IV over 1 minute or via minibag on days 1 and 8. Treatment repeats every 28 days in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 2 years, and then annually for 6 years.
View this trial on ClinicalTrials.gov
