Clinical Trial: Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

Brief 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 tumor 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. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor 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 tumor cells and may also reduce the late side effects of treatment.

Detailed Summary:

PRIMARY OBJECTIVES:

I. 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 radiotherapy (CSI) (18 Gray [Gy]) with a limited target volume boost to the tumor bed of 36 Gy for a total of 54 Gy and reduced chemotherapy approach (no vincristine [vincristine sulfate] during radiotherapy 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 result in "real-time" classification of WNT-driven medulloblastoma.

II. To use the ALTE07C1 protocol to prospectively evaluate and longitudinally model the cognitive, social, emotional and behavioral functioning of children who are treated with reduced CSI (18 Gy) with a limited target volume boost to the tumor bed (to a total of 54 Gy) and reduced chemotherapy (reduced cisplatin, vincristine and lomustine [CCNU]).

TERTIARY OBJECTIVES:

I. 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.

PFS along with the confidence intervals will be estimated using the Kaplan-Meier method. PFS will also be reported based on central radiology review.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in neurocognitive function (cognitive, social, emotional and behavioral) according to Children Oncology Group Standard Neuropsychological Battery [ Time Frame: Baseline to up to 60 months post-diagnosis ]
    Neurocognitive function will be measured at 9, 30 and 60 months post diagnosis and will be compared with the neurocognitive outcomes from an age and gender matched ACNS0331 cohort to the WNT patients treated on ACNS1422. Data for all assessments will be available as standardized t-scores. The change over time for each component of the neuropsychological testing will be estimated using the Generalized Estimating Equation (GEE) approach, with the standardized t-scores as the dependent variable and the assessment times as a covariate. Within the ACNS1422 cohort GEE models will also be used to exp
  • DNA methylation profiling as real-time classification of WNT-driven medulloblastoma [ Time Frame: Within 32 days of definitive surgery ]
    Results will be compared to the results of the molecular screening tests. The sensitivity and specificity comparison between DNA methylation arrays and the standard methods (molecular screening tests for WNT using IHC and CTNNB1 sequencing) will be performed using McNemar's test.


Original Secondary Outcome: Same as current

Information By: Children's Oncology Group

Dates:
Date Received: March 25, 2016
Date Started: October 2016
Date Completion:
Last Updated: September 23, 2016
Last Verified: September 2016