Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
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Purpose
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Untreated Childhood Medulloblastoma Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor |
Drug: etoposide Drug: cyclophosphamide Drug: cisplatin Biological: filgrastim Drug: carboplatin Drug: thiotepa Drug: methotrexate Drug: leucovorin calcium Drug: vincristine sulfate Procedure: autologous hematopoietic stem cell transplantation Other: laboratory biomarker analysis Procedure: quality-of-life assessment |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children <36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue Versus the Same Therapy Without Methotrexate |
- Complete response (CR) rate [ Time Frame: From baseline to up to 4 years ] [ Designated as safety issue: No ]The analysis of response will be based on a one-sided, two-sample test of proportions, with Type I error of 10%. Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transverse (T), and length (L) measurements.
- Time to treatment failure defined as disease progression or recurrence, death from any cause, or occurrence of a second malignant neoplasm [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: No ]
The analysis of event-free survival (EFS) will be based on a proportional hazards, non-mixture parametric cure model (PCM).
Partial stratification will be accomplished by separately estimating the scale parameter of the Weibull kernel function within each of the patient arms.
- Toxicity rates of acute, chronic, and late effects of the two intense regimens [ Time Frame: From the beginning of treatment to end of study, assessed up to 4 years ] [ Designated as safety issue: Yes ]Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Patients who have progression or recurrence of disease will be censored in these analyses. Differences in incidence for treatment regimens will be tested with the log-rank test for overall pattern.
- Rates of gastrointestinal and nutritional toxicities [ Time Frame: In each course or treatment ] [ Designated as safety issue: Yes ]Rates of gastrointestinal and nutritional toxicities will be summarized using standard descriptive statistical methods. The two groups will be compared using a Chi-square test to detect a significant difference in complications between the two groups.
- Quality of life and neuropsychological (NP) scores as assessed by the Children Oncology Group (COG) Standard Neuropsychological and Behavioral Battery [ Time Frame: From baseline to up to 4 years ] [ Designated as safety issue: No ]Parent-report questionnaires will be completed to gather information about the patient's function, specifically in terms of attention, memory, executive abilities, and behavioral/social/emotional adaptation. Long-term effects of treatment on neuropsychological and quality of life outcomes will be primarily descriptive. Correlational analyses will be conducted, with Pearson product moment correlations computed for continuous data and chi-square analyses conducted for discrete data.
- Gene expression profiling by northern blotting or by gel electrophoresis [ Time Frame: At baseline ] [ Designated as safety issue: No ]The methods used by Golub and colleagues and Pomeroy and colleagues, as well as standard statistical techniques such as Cox regression analysis will be used in these analyses. Internal cross-validation procedures, such as the leave-one-out method, will be utilized in the training set to provide less-biased estimates of correct classification rates.
| Estimated Enrollment: | 96 |
| Study Start Date: | August 2007 |
| Estimated Primary Completion Date: | September 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I (induction+consolidation chemotherapy, autologous PBSC))
Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. |
Drug: etoposide
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Biological: filgrastim
Given IV or SC
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: thiotepa
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplantation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
|
|
Experimental: Arm II (induction+consolidation chemotherapy, autologous PBSC)
Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. |
Drug: etoposide
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Biological: filgrastim
Given IV or SC
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: thiotepa
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Drug: leucovorin calcium
Given IV or orally
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplantation
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
|
Show Detailed Description Eligibility| Ages Eligible for Study: | up to 2 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diagnosis of 1 of the following:
High-risk medulloblastoma defined by any of the following:
- Residual disease > 1.5 cm²
- Lumbar cerebral spinal fluid cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or ≥ 10 days after definitive surgery unless contraindicated
- M0 disease in children < 8 months of age at diagnosis
- M2 or M3 metastatic disease by MRI
- M4 disease
- Supratentorial primitive neuroectodermal tumor (PNET)(any M-stage)
- Anaplastic medulloblastoma regardless of M-stage or residual tumor
- M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2
- MRI evidence of spinal disease
- Tumor must be negative for INI1 gene
- Has undergone definitive surgery within the past 31 days
- No atypical teratoid rhabdoid tumors
- Biological specimens must be available for correlative laboratory studies
- Life expectancy > 8 weeks
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT < 2 times ULN
- Shortening fraction ≥ 27% by echocardiogram
- Ejection fraction ≥ 47% by radionuclide angiogram
- No evidence of dyspnea at rest
- Pulse oximetry > 94% on room air
- Absolute neutrophil count > 1,000/mm³
- Platelet count > 100,000/mm³ (transfusion independent)
- Hemoglobin > 8 g/dL (RBC transfusions allowed)
- Prior corticosteroids allowed
- No prior radiation therapy or chemotherapy
Contacts and Locations
Show 136 Study Locations| Principal Investigator: | Claire Mazewski | Children's Oncology Group |
More Information
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00336024 History of Changes |
| Other Study ID Numbers: | ACNS0334, NCI-2009-00338, COG-ACNS0334, CDR0000483683, U10CA098543 |
| Study First Received: | June 8, 2006 |
| Last Updated: | June 10, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Glioma Neoplasms, Neuroepithelial Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Etoposide phosphate Cisplatin Cyclophosphamide Etoposide Methotrexate |
Thiotepa Vincristine Carboplatin Lenograstim Leucovorin Levoleucovorin Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating |
ClinicalTrials.gov processed this record on June 17, 2013