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:
Secondary Outcome:
- 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 OBJECTIVES:
·
To estimate the progression-free survival (PFS)
of children >= 3 years of age with wingless-type MMTV integration site
family (WNT)/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:
·
To prospectively test the hypothesis that
deoxyribonucleic acid (DNA) methylation profiling will result in “real-time”
classification of WNT-driven medulloblastoma.
·
To use the ALTE07C1 protocol to prospectively
evaluate and longitudinally model the cognitive, social, emotional and
behavioural 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]).
TERTIARY OBJECTIVES:
·
To explore whether DNA methylation profiling of
medulloblastoma samples will result in a ?real-time? predictive classification
scheme for the Sonic Hedgehog (SHH), Group 3 and Group 4 medulloblastoma
subgroups according to the Heidelberg classifier.
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
