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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ClinicalTrials.gov Identifier: NCT00336024 |
Recruitment Status
:
Completed
First Posted
: June 12, 2006
Last Update Posted
: November 8, 2017
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Tracking Information | ||||
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First Submitted Date ICMJE | June 8, 2006 | |||
First Posted Date ICMJE | June 12, 2006 | |||
Last Update Posted Date | November 8, 2017 | |||
Study Start Date ICMJE | August 2007 | |||
Actual Primary Completion Date | December 31, 2016 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Complete response (CR) rate [ Time Frame: From baseline to up to 9 years ] At the end of consolidation, the number of evaluable patients treated with intensive chemotherapy with methotrexate who achieved CR or not will be compared to those who achieved CR or not after treated with the same intensive chemotherapy without methotrexate. The CR rates between these two groups will be compared at a significance level of 0.1 using one-sided Chi-square test.
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Original Primary Outcome Measures ICMJE | Not Provided | |||
Change History | Complete list of historical versions of study NCT00336024 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma | |||
Official Title ICMJE | 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 | |||
Brief Summary | 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. | |||
Detailed Description | PRIMARY OBJECTIVES: I. Determine if treatment of pediatric patients with newly diagnosed supratentorial primitive neuroectodermal CNS tumors or high-risk medulloblastoma with intensive induction chemotherapy comprising vincristine, etoposide, cyclophosphamide, and cisplatin in combination with high-dose methotrexate and leucovorin calcium followed by consolidation chemotherapy comprising carboplatin and thiotepa and peripheral blood stem cell rescue results in a higher complete response rate then in patients treated with the same regimen without high-dose methotrexate and leucovorin calcium. SECONDARY OBJECTIVES: I. Determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs. II. Compare event-free survival and patterns of failure in patients treated with these regimens. III. Compare the acute, chronic, and late effects of these regimens, particularly in terms of tolerance to the same consolidation regimen after treatment with 2 different induction regimens, in these patients. IV. Compare the gastrointestinal and nutritional toxicities of these regimens in these patients. V. Compare the quality of life outcomes in patients treated with these regimens. VI. Compare the neuropsychological effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to diagnosis* (M0 medulloblastoma with ≥ 1.5 cm² residual tumor vs M1 medulloblastoma [positive lumbar CSF cytology] vs M2, M3, or M4 medulloblastoma vs supratentorial PNET [any M-stage] vs M0 medulloblastoma < 8 months without residual disease or with < 1.5 cm² radiographic measurable residual tumor vs anaplastic M0 medulloblastoma without residual disease or with < 1.5 cm² radiographic measurable residual vs classic M0 (nondesmoplastic) medulloblastoma with < 1.5 cm² radiographic measurable residual tumor). NOTE: *All diagnoses are for children < 36 months unless otherwise noted. INDUCTION THERAPY: Patients are randomized to 1 of 2 induction treatment arms. ARM I: Patients receive vincristine 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; and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive vincristine 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. Once 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. Patients also receive G-CSF IV or SC beginning 24 hours after the completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. In both arms, patients with stable disease or partial response after induction therapy proceed to second-look surgery followed by consolidation therapy. Patients with a complete response after induction therapy proceed directly to consolidation therapy. CONSOLIDATION THERAPY: Beginning no more than 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 G-CSF IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous peripheral blood stem cells (PBSC) IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Blood and tissue samples are collected at baseline for correlative studies, including gene expression profiling, biological marker analysis (i.e., cMyc, ErbB2/ErbB4), comparative genome analysis, and mutation analysis. After completion of study therapy, patients are followed up periodically for 4 years and then annually thereafter. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 3 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Estimated Enrollment ICMJE |
96 | |||
Original Enrollment ICMJE | Not Provided | |||
Actual Study Completion Date | December 31, 2016 | |||
Actual Primary Completion Date | December 31, 2016 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
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Sex/Gender |
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Ages | up to 2 Years (Child) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Australia, Canada, Puerto Rico, United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT00336024 | |||
Other Study ID Numbers ICMJE | ACNS0334 NCI-2009-00338 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-ACNS0334 ( Other Identifier: Children's Oncology Group ) U10CA098543 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | Children's Oncology Group | |||
Study Sponsor ICMJE | Children's Oncology Group | |||
Collaborators ICMJE | National Cancer Institute (NCI) | |||
Investigators ICMJE |
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PRS Account | Children's Oncology Group | |||
Verification Date | February 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |