Radiation Therapy and Combination Chemotherapy for Medulloblastoma

Study Overview
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Brief Summary
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This phase II trial is studying giving radiation therapy together with combination chemotherapy after surgery to see how well it works in treating children with newly diagnosed medulloblastoma.

Detailed Description
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OUTLINE: Adjuvant induction chemoradiotherapy: Beginning within 28 days after prior resection, patients undergo radiotherapy to the craniospinal axis 5 days a week for 4 weeks and then conformal radiotherapy to the tumor bed 5 days a week for 2 weeks. Beginning 1 week after the initiation of radiotherapy, Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. Maintenance chemotherapy: Beginning 4 weeks after the completion of induction chemoradiotherapy, patients receive eight 4-week cycles of temozolomide (dosage: the 1st cycle, 150mg/m2, daily × 5 days, 4 weeks a cycle; the 2-8th cycle, 200mg/m2, daily × 5 days, 4 weeks a cycle and repeated again). PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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Phase 2 Study of Radiation Therapy and Combination Chemotherapy Following Surgery in Treating Children With Newly Diagnosed Medulloblastoma

Conditions
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Medulloblastoma

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: Craniospinal Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed posterior fossa medulloblastoma No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI No tumor in the spinal or cerebral subarachnoid space by MRI No tumor in the subarachnoid space by Cerebrospinal fluid (CSF) No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively Must begin radiotherapy on study within 28 days after surgery Exclusion Criteria: Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed. Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator. Patients with the following will not be eligible: > 1.5cm3 residual tumor following resection as indicated by post-operative MRI. tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine tumor in subarachnoid space by CSF cytology failure to perform staging studies (spine MRI, CSF cytology) either pre- or post- operatively

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Treatment<br>All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with Temozolomide. Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation therapy are combined as Temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles. | Drug: Temozolomide<br>* Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles (dosage: the 1st cycle, 150mg/m2, daily × 5 days, 4 weeks a cycle; the 2-8th cycle, 200mg/m2, daily × 5 days, 4 weeks a cycle and repeated again).<br>* Other names: brand names Temodar and Temodal and Temcad;Radiation: Craniospinal Radiation<br>* Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (Temozolomide).<br>* Other names: Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | first analysis will occur 1 month after accrual of all patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Overall survival (OS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Evaluate Rate of Late Neurotoxic Effects | Evaluate the late neurotoxic effects of low dose craniospinal radiation, including cognitive, endocrinologic and auditory function. | 3 years |