NCT02724579

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

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

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 description

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 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 accurately classify WNT-driven medulloblastoma. II. To prospectively evaluate and longitudinally model the cognitive, social, emotional, behavioral, and quality of life (QoL) 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 \[CCNU\]). 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 tumor 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) 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 via minibag on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) throughout the trial. 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.

Conditions

• Medulloblastoma

Interventions

Type	Name	Description
DRUG	Cisplatin	Given IV
DRUG	Cyclophosphamide	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Lomustine	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
RADIATION	Radiation Therapy	Undergo craniospinal radiation therapy
DRUG	Vincristine	Given IV or via minibag
DRUG	Vincristine Sulfate	Given IV or via minibag

Timeline

• Start date: 2017-11-17
• Primary completion: 2028-03-31
• Completion: 2028-03-31
• First posted: 2016-03-31
• Last updated: 2026-02-17

Locations

195 sites across 5 countries: United States, Australia, Canada, Puerto Rico, Saudi Arabia

Regulatory

• FDA-regulated device study