Brain and Central Nervous System Tumors
Conditions
Keywords
adult medulloblastoma, untreated childhood medulloblastoma
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.
Interventions
DRUGcisplatin
DRUGlomustine
DRUGvincristine sulfate
PROCEDUREadjuvant therapy
RADIATIONiodine I 131 monoclonal antibody 3F8
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility | 2 years |
| Progression-free Survival | 2 years |
| Morbidity | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Histologic Proof of Medulloblastoma This is a single-arm study of post-operative radioimmunotherapy (intrathecal 131-I-3F8), reduced-dose craniospinal radiation therapy (1800 cGy), primary site boost (to 5400 cGy) via IMRT and standard chemotherapy. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Histologic Proof of Medulloblastoma |
|---|---|
| Age, Continuous | 6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
Feasibility
Time frame: 2 years
Population: No data were collected
Primary
Morbidity
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Histologic Proof of Medulloblastoma | Morbidity | Deceased | 3 Participants |
| Histologic Proof of Medulloblastoma | Morbidity | Alive | 3 Participants |
Primary
Progression-free Survival
Time frame: 2 years
Population: Data were not collected