Anaplastic Medulloblastoma, Medulloblastoma
Conditions
Brief summary
This phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Chemotherapy drugs, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, 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 more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients. II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients. CORRELATIVE SCIENCE OBJECTIVES: I. To compare residual disease response to radiation alone versus radiation plus carboplatin. II. To identify molecular prognostic indicators suitable for patient stratification in future trials. III. To evaluate the health-related quality of life (HRQOL) during phases of active treatment specific to treatment modalities. IV. To describe the neuropsychological functioning of the study population and to evaluate the relationship between neuropsychological status and health related quality of life. OUTLINE: Patients are randomized to Arm A or Arm B (Arms C and D closed to accrual as of Amendment 3 1/27/15). ARM A (standard chemoradiotherapy and standard maintenance therapy): CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD) five days a week for 6 weeks. Patients also receive vincristine sulfate intravenously (IV) over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim subcutaneously (SC) or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, lumbar puncture and magnetic resonance imaging (MRI) throughout the study. ARM B (standard chemoradiotherapy plus carboplatin and standard maintenance therapy): CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm I. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm I. Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study. ARM C (standard chemoradiotherapy, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin - CLOSED TO ACCRUAL 1/27/15): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin orally (PO) twice daily (BID) on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm I maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM D (standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin - CLOSED TO ACCRUAL 1/27/15): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm III. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm III. After completion of study treatment, patients are followed up periodically for 1 year.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood sample collection
DRUGCarboplatin
Given IV
DRUGCisplatin
Given IV
DRUGCyclophosphamide
Given IV
BIOLOGICALFilgrastim
Given IV or SC
DRUGIsotretinoin
Given PO
PROCEDURELumbar Puncture
Undergo lumbar puncture
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
OTHERQuality-of-Life Assessment
Ancillary studies
RADIATIONRadiation Therapy
Undergo radiation therapy
DRUGVincristine Sulfate
Given IV
Sponsors
Children's Oncology Group
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 22 Years
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to 3 and less than 22 years at the time of diagnosis * Newly diagnosed, previously untreated: (1) M0 medulloblastoma with \> 1.5 cm\^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor * As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued * All patients with M4 disease are not eligible * A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility since radiation therapy planning and response will be based on MRI scans only * Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory * Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred because surgically-induced inflammation/blood can be difficult to distinguish from tumor * Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained \> 7 days post-operatively (to rule out surgically induced false positives) * Patients must have a Karnofsky performance level of \>= 30 for patients \> 16 years of age or a Lansky performance scale of \>= 30 for patients =\< 16 years of age and life expectancy \> 8 weeks * No previous chemotherapy or radiation therapy * Corticosteroids should not be used during chemotherapy administration as an antiemetic because of their effect on the blood-brain barrier * Clinically significant drug interactions have been reported when using vincristine with strong CYP450 3A4 inhibitors and inducers. Selected strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (cytochrome P450 3A4) include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine (vincristine sulfate) * The clinical outcome and significance of CYP450 interactions with cyclophosphamide are less clear. CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution; aprepitant also interacts with CYP3A4 and should be used with caution with etoposide or vincristine chemotherapy * Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity * In patients receiving cisplatin and phenytoin or fosphenytoin, serum concentrations of phenytoin may decrease. Carbamazepine concentration may also decrease with concomitant use. Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin * No other experimental therapy is permitted while on study * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/gender as follows: * 0.8 mg/dL (2 to \< 6 years of age) * 1.0 mg/dL (6 to \< 10 years of age) * 1.2 mg/dL (10 to \< 13 years of age) * 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age) * 1.7 mg/dL (male) or 1.4 mg/dL (female) (\>= 16 years of age) * Total bilirubin \< 1.5 x upper limit of normal (ULN) for age * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for patients on anti-seizure medications, SGOT (AST) or SGPT (ALT) must be \< 5 x ULN * Absolute neutrophil count (ANC) \>= 1,000/uL * Platelets \>= 100,000/uL (untransfused) * Hemoglobin \>= 8 g/dl (may be transfused) * There is information indicating a risk of fetal or teratogenic toxicity with this treatment. Female patients who are post-menarchal must have a negative pregnancy test; lactating female patients must agree not to breast-feed while on this trial; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma | Up to 5 years | The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined. |
| Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | Up to 5 years | The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response to Radiation Therapy for Patients With Medulloblastoma | 12 weeks after treatment initiation | Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. |
| Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 12 weeks after treatment initiation | Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335. |
| Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma | Up to 5 years | The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined. |
| Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | Up to 5 years | The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. |
| The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 6 - 12 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients | 24 - 36 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients | 48 - 72 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients | 6 - 12 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients | 24 - 36 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients | 48 - 72 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 6 - 12 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients | 24 - 36 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients | 48 - 72 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients | 6 - 12 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients | 24 - 36 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. |
| Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients | 48 - 72 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. |
Countries
Australia, Canada, Netherlands, Puerto Rico, United States
Contacts
PRINCIPAL_INVESTIGATORSarah E Leary
Children's Oncology Group
Participant flow
Recruitment details
Patients (Pts) 3-21 yrs were recruited at COG institutions.The first pt was enrolled 5/23/2007, and the last pt was enrolled 4/9/2018.The study was initially open to medulloblastoma and supratentorial primitive neuroectodermal tumor (SPNET) pts, but closed for SPNET pts as of amendment #2.All pts were off treatment at the time of results reporting.
Pre-assignment details
Participants received standard therapy consisting of surgery, radiation and chemotherapy. A subset of patients was randomly assigned to receive carboplatin. A second randomization was used to randomly assign patients to receive isotretinoin. Of note, the isotretinoin randomization was stopped early due to futility.
Participants by arm
| Arm | Count |
|---|---|
| Regimen A (Medulloblastoma Patients) Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin) | 87 |
| Regimen B (Medulloblastoma Patients) Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin) | 89 |
| Regimen C (Medulloblastoma Patients) Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin) | 53 |
| Regimen D (Medulloblastoma Patients) Medulloblastoma patients who received regimen D (carboplatin / isotretinoin) | 56 |
| Regimen A (SPNET Patients) SPNET patients who received regimen A (no carboplatin / no isotretinoin) | 23 |
| Regimen B (SPNET Patients) SPNET patients who received regimen B (carboplatin / no isotretinoin) | 19 |
| Regimen C (SPNET Patients) SPNET patients who received regimen C (no carboplatin / isotretinoin) | 21 |
| Regimen D (SPNET Patients) SPNET patients who received regimen D (carboplatin / isotretinoin) | 22 |
| Total | 370 |
Baseline characteristics
| Characteristic | Regimen B (Medulloblastoma Patients) | Regimen C (Medulloblastoma Patients) | Regimen D (Medulloblastoma Patients) | Regimen A (SPNET Patients) | Regimen B (SPNET Patients) | Regimen C (SPNET Patients) | Regimen A (Medulloblastoma Patients) | Regimen D (SPNET Patients) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 88 Participants | 51 Participants | 55 Participants | 23 Participants | 19 Participants | 21 Participants | 86 Participants | 22 Participants | 365 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Age, Continuous | 8.8 years | 9.1 years | 9 years | 10.7 years | 9.4 years | 8.9 years | 8.2 years | 10.3 years | 8.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 10 Participants | 13 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants | 2 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 41 Participants | 42 Participants | 20 Participants | 15 Participants | 18 Participants | 75 Participants | 19 Participants | 309 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 0 Participants | 9 Participants | 2 Participants | 3 Participants | 12 Participants | 8 Participants | 46 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 6 Participants | 1 Participants | 2 Participants | 4 Participants | 10 Participants | 2 Participants | 39 Participants |
| Race (NIH/OMB) White | 69 Participants | 38 Participants | 49 Participants | 13 Participants | 13 Participants | 10 Participants | 63 Participants | 12 Participants | 267 Participants |
| Sex: Female, Male Female | 29 Participants | 15 Participants | 21 Participants | 13 Participants | 10 Participants | 12 Participants | 22 Participants | 12 Participants | 134 Participants |
| Sex: Female, Male Male | 60 Participants | 38 Participants | 35 Participants | 10 Participants | 9 Participants | 9 Participants | 65 Participants | 10 Participants | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 24 / 87 | 23 / 89 | 22 / 53 | 16 / 56 | 11 / 23 | 8 / 19 | 14 / 21 | 8 / 22 |
| other Total, other adverse events | 72 / 87 | 80 / 89 | 47 / 53 | 52 / 56 | 21 / 23 | 18 / 19 | 18 / 21 | 18 / 22 |
| serious Total, serious adverse events | 7 / 87 | 11 / 89 | 5 / 53 | 6 / 56 | 2 / 23 | 0 / 19 | 1 / 21 | 0 / 22 |
Outcome results
Primary
Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Time frame: Up to 5 years
Population: Eligible medulloblastoma patients are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma | 57.5 Percent Probability |
| Regimen B (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma | 65.3 Percent Probability |
| Regimen C (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma | 60.3 Percent Probability |
| Regimen D (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma | 70.9 Percent Probability |
Primary
Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals.
Time frame: Up to 5 years
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 52.2 Percent Probability |
| Regimen B (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 52.6 Percent Probability |
| Regimen C (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 19 Percent Probability |
| Regimen D (Medulloblastoma Patients) | Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 63 Percent Probability |
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
Time frame: 24 - 36 months post diagnosis
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time frame: 24 - 36 months post diagnosis
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients | 53.5 T-Score | Standard Deviation 8.27 |
| Regimen B (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients | 75.5 T-Score | Standard Deviation 12.02 |
| Regimen C (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients | 64.5 T-Score | Standard Deviation 2.12 |
| Regimen D (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients | 53.5 T-Score | Standard Deviation 7.55 |
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time frame: 48 - 72 months post diagnosis
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time frame: 48 - 72 months post diagnosis
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients | 56.0 T-Score | Standard Deviation 0 |
| Regimen B (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients | 64.0 T-Score | — |
| Regimen C (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients | 71.5 T-Score | Standard Deviation 10.61 |
| Regimen D (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients | 53.7 T-Score | Standard Deviation 21.2 |
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time frame: 6 - 12 months post diagnosis
Population: Eligible medulloblastoma patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 50.9 T-Score | Standard Deviation 11.32 |
| Regimen B (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 50.2 T-Score | Standard Deviation 11.92 |
| Regimen C (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 50.8 T-Score | Standard Deviation 10.04 |
| Regimen D (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 47.5 T-Score | Standard Deviation 8.25 |
Secondary
Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time frame: 6 - 12 months post diagnosis
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients | 53.8 T-Score | Standard Deviation 15.73 |
| Regimen B (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients | 66.7 T-Score | Standard Deviation 1.53 |
| Regimen C (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients | 46.1 T-Score | Standard Deviation 8.28 |
| Regimen D (Medulloblastoma Patients) | Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients | 64.3 T-Score | Standard Deviation 6.5 |
Secondary
Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma
The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Time frame: Up to 5 years
Population: Eligible medulloblastoma patients are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma | 66.0 Percent Probability |
| Regimen B (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma | 75.9 Percent Probability |
| Regimen C (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma | 69.9 Percent Probability |
| Regimen D (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma | 81.6 Percent Probability |
Secondary
Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact.
Time frame: Up to 5 years
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 60.9 Percent Probability |
| Regimen B (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 57.9 Percent Probability |
| Regimen C (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 35.3 Percent Probability |
| Regimen D (Medulloblastoma Patients) | Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 77.0 Percent Probability |
Secondary
The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 24 - 36 months post diagnosis
Secondary
The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 24 - 36 months post diagnosis
Population: Eligible SPNET patients are included
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients | 83.3 Score on a scale | Standard Deviation 9.98 |
| Regimen B (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients | 57.5 Score on a scale | Standard Deviation 2.12 |
| Regimen C (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients | 83.7 Score on a scale | Standard Deviation 4.04 |
| Regimen D (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients | 88.5 Score on a scale | Standard Deviation 20.95 |
Secondary
The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 48 - 72 months post diagnosis
Secondary
The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 48 - 72 months post diagnosis
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients | 94.8 score on a scale | Standard Deviation 15.55 |
| Regimen B (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients | 48.0 score on a scale | — |
| Regimen C (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients | 87.0 score on a scale | Standard Deviation 5.66 |
| Regimen D (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients | 79.7 score on a scale | Standard Deviation 25.01 |
Secondary
The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 6 - 12 months post diagnosis
Population: Eligible medulloblastoma patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 96.6 Score on a scale | Standard Deviation 20.54 |
| Regimen B (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 89.1 Score on a scale | Standard Deviation 17.45 |
| Regimen C (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 83.5 Score on a scale | Standard Deviation 15.22 |
| Regimen D (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients | 94.8 Score on a scale | Standard Deviation 16.88 |
Secondary
The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time frame: 6 - 12 months post diagnosis
Population: Eligible SPNET patients are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients | 84.6 Score on a scale | Standard Deviation 9.66 |
| Regimen B (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients | 80.3 Score on a scale | Standard Deviation 28.86 |
| Regimen C (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients | 99.3 Score on a scale | Standard Deviation 16.33 |
| Regimen D (Medulloblastoma Patients) | The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients | 90.6 Score on a scale | Standard Deviation 21.9 |
Secondary
Tumor Response to Radiation Therapy for Patients With Medulloblastoma
Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses.
Time frame: 12 weeks after treatment initiation
Population: 83 of 87 eligible Arm A medulloblastoma patients were evaluated for response after induction, as were 85/89, 48/53, and 55/56 arm B, C, and D patients, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Medulloblastoma | 75.9 percentage of patients |
| Regimen B (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Medulloblastoma | 78.8 percentage of patients |
| Regimen C (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Medulloblastoma | 72.9 percentage of patients |
| Regimen D (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Medulloblastoma | 81.8 percentage of patients |
Secondary
Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
Time frame: 12 weeks after treatment initiation
Population: 23 of 23 eligible Arm A SPNET patients were evaluated for response after induction, as were 18/19, 21/21, and 19/22 arm B, C, and D patients, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 69.9 percentage of patients |
| Regimen B (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 83.3 percentage of patients |
| Regimen C (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 66.7 percentage of patients |
| Regimen D (Medulloblastoma Patients) | Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) | 73.7 percentage of patients |