Intrathecal Radioimmunotherapy, Radiation Therapy, and Chemotherapy After Surgery in Treating Patients With Medulloblastoma

OBJECTIVES:

• Determine the feasibility of combining post-operative intrathecal radioimmunotherapy, craniospinal radiotherapy with intensity-modulated radiotherapy boost, and chemotherapy in patients with standard-risk medulloblastoma.
• Determine whether this regimen can maintain or exceed the current progression-free survival rate while decreasing long-term serious morbidity in these patients.
• Determine the long-term morbidities, most specifically neuropsychological, neuroendocrine, audiometric, and growth outcomes, in patients treated with this regimen.

OUTLINE:

• Radioimmunotherapy: Patients receive intrathecal iodine I 131 monoclonal antibody 3F8 on days 1 and 8.
• Radiotherapy: Beginning as soon as possible after radioimmunotherapy, patients undergo external-beam and intensity-modulated radiotherapy 5 days a week for 6 weeks.
• Chemotherapy: Patients receive vincristine IV once weekly for 8 weeks concurrently with radiotherapy. Beginning about 6 weeks after completion of radiotherapy (4 weeks after vincristine), patients receive cisplatin IV over 6 hours and oral lomustine on day 0 and vincristine IV on days 0, 7, and 14. Treatment repeats every 6 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study within 3.2 years.

Inclusion criteria

• Patients must have histologic proof of medulloblastoma reviewed by the Department of Pathology at the Memorial Sloan-Kettering Cancer Center.
• Patients must begin study prescribed therapy within 42 days of neurosurgical resection of the tumor
• Age ≥ 3-years-old. Post-operative head MRI must confirm ≤ 1.5 cm2 of residual tumor is present.
• Head and spine MRI and lumbar CSF cytology must not show any definitive evidence of leptomeningeal dissemination (Chang stage M-0).
• Examinations evaluating extra-neural sites will not be mandated, but any performed for clinical indications must be free of metastatic disease.
• No prior RT or chemotherapy for the medulloblastoma is permitted Patients must have adequate CSF flow (defined as lack of compartmentalization) on an 111-Indium DTPA flow study.
• Patients must have adequate organ function as defined by:
• Hepatic: total bilirubin < 2.0 mg/dl, AST < 3 x the upper limit of normal.
• Renal: Calculated creatinine clearance or nuclear GFR ≥ 70 ml/min/1.73 m^2.
• The patient, or for minors, a parent or legal guardian, must give informed written consent indicating they are aware of the investigational nature of this study.

Exclusion criteria

• Unable to start study prescribed therapy within 42 days of neurosurgical resection of the tumor
• Age less than 3 years > 1.5 cm2 residual tumor on post-operative head MRI
• Evidence of leptomeningeal dissemination on head or spine MRI or CSF cytology positivity
• Evidence of extra-neural metastases
• Prior radiation therapy or chemotherapy for the medulloblastoma
• Inadequate CSF flow on 111-Indium DTPA flow study Patients with signs or symptoms suggestive of increased intracranial pressure (headache, emesis, ocular paresis) will not be eligible until they are cleared by neurology and/or neurosurgery.
• Pregnancy
• Total bilirubin ≥ 2.0 mg/dl
• AST ≥ 3 x the upper limit of normal
• Creatinine clearance and GFR < 70 ml/min/1.73 m^2