Phase 3
N=91
Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
Anaplastic Medulloblastoma · Medulloblastoma · Supratentorial Embryonal Tumor, Not Otherwise Specified · Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
Bottom Line
View on ClinicalTrials.gov: NCT00336024 ↗Enrolled (actual)
91
Serious AEs
14.3%
Results posted
Oct 2018
Primary outcome: Primary: Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate — 13; 15; 16; 15 Participants — p=0.35
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Autologous Hematopoietic Stem Cell Transplantation (Procedure); Carboplatin (Drug); Cisplatin (Drug); Cyclophosphamide (Drug); Etoposide (Drug); Filgrastim (Biological); Laboratory Biomarker Analysis (Other); Leucovorin Calcium (Drug); Methotrexate (Drug); Quality-of-Life Assessment (Other); Thiotepa (Drug); Vincristine Sulfate (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Dec 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate |
13; 15; 16; 15 | 0.35 |
| SECONDARY Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort |
5; 6; 15; 10; 0; 2 | — |
| SECONDARY Percentage of Participants With Event Free Survival (EFS) |
43.6; 52.6 | 0.28 |
| SECONDARY Patterns of Failure |
7; 6; 8; 7; 5; 3 | 1.00 |
| SECONDARY Percentage of Participants With Any Acute Adverse Events |
97.4; 97.2 | 0.74 |
| SECONDARY Number of Participants With Acute Hearing Loss and No Acute Hearing Loss |
7; 6; 32; 32 | 1.00 |
| SECONDARY Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism |
3; 5 | — |
| SECONDARY Number of Participants With Chronic Central Hypothyroidism |
1; 1 | — |
| SECONDARY Number of Participants With Chronic Low Somatomedin C |
2; 5 | — |
| SECONDARY Number of Participants With Chronic Diabetes Insipidus |
1; 1 | — |
| SECONDARY Number of Participants With Secondary Malignancies |
1; 0 | — |
| SECONDARY Number of Participants With Chronic/Late Hearing Loss and No Chronic/Late Hearing Loss |
12; 13; 27; 25 | 0.8 |
| SECONDARY Rates of Gastrointestinal Toxicities |
8; 12; 31; 26; 4; 10 | 0.27 |
| SECONDARY Rates of Nutritional Toxicities |
10; 17; 29; 21; 13; 13 | 0.08 |
| SECONDARY Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI). |
60.5; 56.5; 77.0; 78.5; 82.0; 89.0 | — |
Summary
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma when given before additional intense chemotherapy followed by peripheral blood stem cell rescue. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.
Eligibility Criteria
Inclusion Criteria
- High-risk medulloblastoma defined by any of the following:
- > 1.5 cm^2 residual disease for any medulloblastoma histology, or
- Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or
- Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or
- M4 disease
- Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry
- Children less than 8 months of age at the time of definitive surgery with or without measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible for study entry
- Patients with anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
- Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease 8 weeks
- Patient must have received no prior radiation therapy or chemotherapy other than corticosteroids; corticosteroids are allowable for all patients
- Creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min
- Total bilirubin = = 27% by echocardiogram, or
- Ejection fraction >= 47% by radionuclide angiogram
- No evidence of dyspnea at rest
- Pulse oximetry > 94% on room air
- Peripheral absolute neutrophil count (ANC) > 1,000/uL
- Platelet count > 100,000/uL (transfusion independent)
- Hemoglobin greater than 8 g/dL (may have received red blood cell [RBC] transfusions allowed)
- Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
- Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal excretion of methotrexate is inhibited by these agents
- Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)
- Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine) should be avoided
- Clinically significant drug interactions have been reported when using vincristine with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors and inducers; selected strong inhibitors of 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
- 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
Data sourced from ClinicalTrials.gov (NCT00336024). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.