Clinical trial NCT00058370: Intrathecal Radioimmunotherapy, Radiation Therapy, and Chemotherapy After Surgery in Treating Patients With Medulloblastoma
Official title: A Trial Of Radioimmunotherapy, Reduced-Dose External Beam Craniospinal Radiation Therapy With IMRT Boost, And Chemotherapy For Patients With Standard-Risk Medulloblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain and Central Nervous System Tumors
Keywords: adult medulloblastoma
untreated childhood medulloblastoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-04-09
Enrollment: 6
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radioimmunotherapy uses radiolabeled monoclonal antibodies to locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining intrathecal radioimmunotherapy and radiation therapy with combination chemotherapy may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of combining intrathecal radioimmunotherapy and radiation therapy with combination chemotherapy in treating patients who have undergone surgery for medulloblastoma.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility
timeFrame: 2 years
measure: Progression-free Survival
timeFrame: 2 years
measure: Morbidity
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ira Dunkel, MD
role: STUDY_CHAIR
References: