Ignite Creation Date:
2025-12-24 @ 10:14 PM
Ignite Modification Date:
2025-12-28 @ 6:11 PM
Study NCT ID:
NCT00085735
Status:
COMPLETED
Last Update Posted:
2025-01-14
First Post:
2004-06-14
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
Sponsor:
Children's Oncology Group
Organization:
Study Overview
Official Title:
A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial
Status:
COMPLETED
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine whether reducing the craniospinal dose of radiation therapy to 18.00 Gy in children 3-7 years of age does not compromise event-free survival and overall survival as compared to treatment with 23.40 Gy of craniospinal radiation; and to determine if reducing the irradiated volume of the primary site tumor boost from the whole posterior fossa to the tumor bed only will not compromise event-free and overall survival.
SECONDARY OBJECTIVES:
I. To evaluate patterns of failure in children treated with an irradiation boost volume smaller than conventional posterior fossa volumes.
II. To reduce the cognitive, auditory and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy.
III. To determine if the audiologic and endocrinologic toxicity will be reduced with the use of limited tumor boost volume irradiation compared to patients treated with conventional target volumes of radiation.
IV. To develop an optimal gene expression medulloblastoma outcome predictor, validated prospectively in a multi-institution randomized clinical trial.
V. To improve compliance with long-term quality of life and functional status data submission by educating institutional nurses to administer and submit for analysis a battery of four instruments: Behavior Assessment System for Children- 2nd Edition (BASC-2), Adaptive Behavior Assessment System - 2nd Edition (ABAS-II), Behavior Rating Inventory of Executive Function (BRIEF), PedsQLTM 4.0.
OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).
Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).
ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.
ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.
ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.
ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.
ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.
ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.
MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.
REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.
Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).
Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).
ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.
ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.
ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.
ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.
ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.
ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.
MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.
REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.
Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
I. To determine whether reducing the craniospinal dose of radiation therapy to 18.00 Gy in children 3-7 years of age does not compromise event-free survival and overall survival as compared to treatment with 23.40 Gy of craniospinal radiation; and to determine if reducing the irradiated volume of the primary site tumor boost from the whole posterior fossa to the tumor bed only will not compromise event-free and overall survival.
SECONDARY OBJECTIVES:
I. To evaluate patterns of failure in children treated with an irradiation boost volume smaller than conventional posterior fossa volumes.
II. To reduce the cognitive, auditory and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy.
III. To determine if the audiologic and endocrinologic toxicity will be reduced with the use of limited tumor boost volume irradiation compared to patients treated with conventional target volumes of radiation.
IV. To develop an optimal gene expression medulloblastoma outcome predictor, validated prospectively in a multi-institution randomized clinical trial.
V. To improve compliance with long-term quality of life and functional status data submission by educating institutional nurses to administer and submit for analysis a battery of four instruments: Behavior Assessment System for Children- 2nd Edition (BASC-2), Adaptive Behavior Assessment System - 2nd Edition (ABAS-II), Behavior Rating Inventory of Executive Function (BRIEF), PedsQLTM 4.0.
OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).
Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).
ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.
ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.
ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.
ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.
ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.
ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.
MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.
REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.
Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).
Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).
ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.
ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.
ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.
ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.
ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.
ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.
MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.
REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.
Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2009-00335 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| ACNS0331 | None | None | View | |
| 12238 | None | None | View | |
| COG-ACNS0331 | None | None | View | |
| CDR0000365506 | None | None | View | |
| ACNS0331 | OTHER | Children's Oncology Group | View | |
| ACNS0331 | OTHER | CTEP | View | |
| U10CA180886 | NIH | None | https://reporter.nih.gov/quic… | View |
| U10CA098543 | NIH | None | https://reporter.nih.gov/quic… | View |