Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
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| ClinicalTrials.gov Identifier: NCT00085735 |
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Recruitment Status :
Active, not recruiting
First Posted : June 16, 2004
Results First Posted : June 14, 2017
Last Update Posted : February 28, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Untreated Childhood Medulloblastoma | Drug: Cisplatin Radiation: Craniospinal Irradiation Drug: Cyclophosphamide Radiation: Involved-Field Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Lomustine Other: Quality-of-Life Assessment Radiation: Radiation Therapy Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 549 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | April 2004 |
| Actual Primary Completion Date : | March 31, 2016 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Craniospinal Irradiation Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Radiation: Involved-Field Radiation Therapy Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Craniospinal Irradiation Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Craniospinal Irradiation Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Radiation: Involved-Field Radiation Therapy Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
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Radiation: Craniospinal Irradiation
Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Craniospinal Irradiation Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Radiation: Involved-Field Radiation Therapy Undergo smaller volume boost (involved-field radiation therapy)
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Craniospinal Irradiation Undergo craniospinal Irradiation Drug: Cyclophosphamide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lomustine Given orally
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo standard volume boost (whole posterior fossa radiation therapy)
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Event-free Survival (EFS) [ Time Frame: Assessed at 3 years ]EFS was defined as the time interval from date of study entry to date of disease progression, disease recurrence, second malignant neoplasm or death from any cause, whichever occurs first, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% confidence intervals (CI's).
- Overall Survival (OS) [ Time Frame: 3 years ]OS was defined as the time interval from date of study entry to date of death from any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. For purposes of this analysis, arms I, III and V (involved field radiation therapy [IFRT]) are combined and compared to arms II, IV and VI (posterior fossa irradiation [PFRT]).
Secondary Outcome Measures :
- Local Posterior Fossa (LPF) Failure Rate [ Time Frame: 3 years ]LPF failure was defined as tumor recurrence/progression within the tumor bed. The cumulative incidence (CI) of LPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF) and with other events prior to LPF failure (e.g., death, second malignancy) were considered as having competing events.
- Non-local Posterior Fossa (NLPF) Failure Rate [ Time Frame: 3 years ]NLPF failure was defined as tumor recurrence/progression outside the radiation therapy clinical target volume boost (CTV-boost) but within the posterior fossa CTV (CTV-PF). The cumulative incidence (CI) of NLPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF, LPF) and with other events prior to NLPF failure (e.g., death, second malignancy) were considered as having competing events.
- Non-posterior Fossa (NPF) Failure Rate [ Time Frame: 3 years ]NPF failure was defined as tumor recurrence within the neuroaxis but outside the radiation therapy clinical target volume (CTV). The cumulative incidence (CI) of NPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., LPF failure) and with other events prior to NPF failure (e.g., death, second malignancy) were considered as having competing events.
- Post-treatment Endocrine Function by CSI Group [ Time Frame: Up to 3 years ]Post-treatment endocrine function was measured by laboratory assessment of the thyroid stimulating hormone (TSH). The mean TSH will be reported.
- Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4 [ Time Frame: Up to 3 years ]Proportions of patients with grade 3+ hearing loss after the completion of therapy will be calculated and reported separately for low dose craniospinal irradiation (LDCSI) versus (vs.) standard dose craniospinal irradiation (SDCSI) patients. Eligible and evaluable patients 3-7 years of age will be used.
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis). [ Time Frame: 4 -15 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 4-15 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better.
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis) [ Time Frame: 27 - 48 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 27-48 months post diagnosis, only the assessments before progression date were reported. The range of FSIQ is 50 - 150. A higher FSIQ is better.
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) [ Time Frame: 49 - 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 49-72 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better.
- Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4 [ Time Frame: Up to 3 years ]Proportions of patients with grade 3+ hearing impairment as assessed by CTCAE v4 at 1-year post treatment were calculated.
- Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group [ Time Frame: Post-treatment up to 3 years ]Endocrine dysfunction was assessed by growth hormone stimulation (GHS) tests. We report the percentage of patients with abnormal growth hormone stimulation tests.
- Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays [ Time Frame: 3 years ]OS was defined as the time interval from date of study entry to date of death from any cause or to date of last contact for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
- Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays [ Time Frame: 3 years ]PFS was defined as the time interval from date of study entry to disease progression, relapse or death due to cancer or to last follow-up. Second malignancies and deaths from causes clearly not associated with tumor progression or recurrence were censored. PFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis) [ Time Frame: 4 - 15 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.
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis) [ Time Frame: 27-48 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.
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) [ Time Frame: 49 - 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.
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis) [ Time Frame: 4-15 months post diagnosis ]Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 4 - 15 months post diagnosis.
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis) [ Time Frame: 27-48 months post diagnosis ]Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 27 - 48 months post diagnosis.
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis) [ Time Frame: 49 - 72 months post diagnosis ]Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 49 - 72 months post diagnosis.
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| Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Histologically confirmed medulloblastoma located in the posterior fossa
- Standard-risk disease
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Minimal volume, non-disseminated disease, defined by the following:
- Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
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No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:
- Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
- Negative cytological examination of CSF after surgery, but before study enrollment
- Brain stem involvement allowed
- Performance status - Karnofsky 50-100% (> 16 years of age)
- Performance status - Lansky 30-100% (≤ 16 years of age)
- Absolute neutrophil count > 1,500/uL
- Platelet count > 100,000/uL (transfusion independent)
- Hemoglobin > 10 g/dL (transfusions allowed)
- Bilirubin < 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 1.5 times ULN for age
- Creatinine clearance OR radioisotope glomerular filtration rate >= 70 mL/min/1.73m^2 or a serum creatinine based on age/gender as follows:
Age Maximum Serum Creatine (mg/dL)
- 1month to < 6 months male: 0.4 female: 0.4
- 6 months to <1 year male: 0.5 female: 0.5
- 1 year to < 2 years male: 0.6 female: 0.6
- 2 to < 6 years male: 0.8 female: 0.8
- 6 to < 10 years male: 1 female: 1
- 10 to < 13 years male: 1.2 female: 1.2
- 13 to < 16 years male: 1.5 female: 1.4
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>= 16 years male: 1.7 female: 1.4
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior chemotherapy
- Prior corticosteroids allowed
- No prior radiotherapy
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00085735
Locations
Show 178 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Jeff Michalski | Children's Oncology Group |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00085735 |
| Other Study ID Numbers: |
ACNS0331 NCI-2009-00335 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-ACNS0331 ACNS0331 CDR0000365506 ACNS0331 ( Other Identifier: Childrens Oncology Group ) ACNS0331 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 16, 2004 Key Record Dates |
| Results First Posted: | June 14, 2017 |
| Last Update Posted: | February 28, 2023 |
| Last Verified: | February 2023 |
Additional relevant MeSH terms:
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Medulloblastoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neuroectodermal Tumors, Primitive Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Cyclophosphamide Lomustine Cisplatin Vincristine |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators |