Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| P01CA021239 | U.S. NIH Grant/Contract | View source | |
| MGH-99-271 | Other Identifier | Massachusetts General Hospital |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
RATIONALE: Specialized radiation therapy that delivers radiation directly to the area where a tumor was surgically removed may kill any remaining tumor cells and cause less damage to normal tissue.
PURPOSE: This phase II trial is studying how well proton beam radiation therapy works in treating young patients who have undergone biopsy or surgery for medulloblastoma or pineoblastoma.
OBJECTIVES:
OUTLINE: Patients are stratified according to risk (standard vs high).
Patients receive proton beam craniospinal and posterior fossa radiotherapy once daily 5 days a week for 6-8 weeks*.
NOTE: *Unless otherwise specified by a co-existing protocol.
Patients undergo neurocognitive evaluation at baseline or within 3 months after completion of radiotherapy and then at 1, 3, and 5 years. Patients also undergo endocrine evaluation at baseline and then annually for 5 years; and audiology evaluation at baseline, before each course of cisplatin-based chemotherapy (if receiving this), and then annually for 5 years.
After completion of study treatment, patients are followed every 3-6 months for 2-5 years.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radiation therapy | Experimental | This is a single arm study of radiation therapy with protons to standard doses. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| radiation therapy | Radiation | Radiation therapy with proton beam to standard doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Ototoxicity | Percentage participants who experienced ototoxicity as measured by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 after the completion of radiation therapy in the overall participant population and by baseline measure subgroups. Incidence is shown after follow-up of 3 years, 5 years, 7 years, and 10 years. | 3 Years, 5 years, 7 years, 10 years |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 3 years of follow-up (as determined by CTCAE 3.0). Incidence is grouped by hormone type and risk group | 3 years |
Not provided
DISEASE CHARACTERISTICS:
Histologically confirmed medulloblastoma or pineoblastoma
Must have undergone biopsy or attempted surgical resection of the tumor within the past 35 days
Requires craniospinal irradiation
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Nancy J. Tarbell, MD | Massachusetts General Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26830377 | Result | Yock TI, Yeap BY, Ebb DH, Weyman E, Eaton BR, Sherry NA, Jones RM, MacDonald SM, Pulsifer MB, Lavally B, Abrams AN, Huang MS, Marcus KJ, Tarbell NJ. Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. Lancet Oncol. 2016 Mar;17(3):287-298. doi: 10.1016/S1470-2045(15)00167-9. Epub 2016 Jan 30. | |
| 30118397 | Derived | Vatner RE, Niemierko A, Misra M, Weyman EA, Goebel CP, Ebb DH, Jones RM, Huang MS, Mahajan A, Grosshans DR, Paulino AC, Stanley T, MacDonald SM, Tarbell NJ, Yock TI. Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors. J Clin Oncol. 2018 Oct 1;36(28):2854-2862. doi: 10.1200/JCO.2018.78.1492. Epub 2018 Aug 17. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Radiation Therapy | radiation therapy: Radiation therapy with proton beam to standard doses |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years |
Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 5 years of follow-up (as determined by CTCAE 3.0). Incidence is shown by hormone type and risk group. |
| 5 years |
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 7 years of follow-up, as determined by CTCAE 3.0. Incidence is shown by hormone type and risk group | 7 years |
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) as determined by CTCAE 3.0) at year 3, year 5, and year 7 of follow-up. | 3 years, 5 years, 7 years |
| Mean Change Per-Year in Neurocognitive Outcomes | The mean change per-year in neurocognitive outcomes as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full Scale Intelligence Quotient (FSIQ) of children with the use of four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale that has an average score of 100 and standard deviation of 15 points in the general population, meaning on average 68% of test takers would be within +/- 15 points of 100 and 95% within +/- 30 points. Higher scores represent higher intelligence and lower score represent reduced intelligence. Participants were assessed for changes in score with the use of repeated testing during a median follow-up time of 5.2 years. Repeated measures were taken at baseline, 1, 3, 5, and 7 years or until the participant was not available for evaluation (whichever comes first). | Baseline, 1, 3, 5, 7 years |
| Progression Free Survival | The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group. | 5 years, 7 years, 10 years |
| Overall Survival | the percentage of participants surviving after five and seven years and at the end of follow-up in the overall population. Survival is shown by risk and histological group. | 5 years, 7 years, 10 years |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Radiation Therapy | radiation therapy: Radiation therapy with proton beam to standard doses |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| ||||||||||||||||||||||
| Age, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| |||||||||||||||||||||||
| Histological Subtype (Dominant Pattern) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Risk Group | Intermediate risk is defined as M0 patients with <1·5 cm² of residual disease but with anaplastic or large cell variant. If residual disease at the primary site was greater than or equal to 1·5 cm² on axial MRI, then they would be classified as high risk if they had no other evidence of metastatic disease. | Count of Participants | Participants |
| ||||||||||||||||||||||
| Posterior Fossa Syndrome | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ventriculoperitoneal Shunt | Count of Participants | Participants |
| |||||||||||||||||||||||
| Enrolled on a Children's Oncology Group Protocol | The alphanumeric codes next to the 'yes' represent Children's Oncology Group protocol numbers | Number | participants |
| ||||||||||||||||||||||
| Boost Field | Count of Participants | Participants |
| |||||||||||||||||||||||
| Boost Dose | Dose measured as Gray (Gy) Relative Biological Effectiveness (RBE) | Count of Participants | Participants |
| ||||||||||||||||||||||
| Craniospinal Radiation Doses | Count of Participants | Participants |
| |||||||||||||||||||||||
| Hypothalamus Mean Dose (D50) | D50 (the half maximal inhibitory dose) is the dose of radiation that is required for 50% inactivation of a tumor cell population. | Count of Participants | Participants |
| ||||||||||||||||||||||
| Cochlear Mean Dose to Each Ear (D50) | Number | Ears |
| |||||||||||||||||||||||
| Cisplatin Cumulative Dose | Cisplatin cumulative dose information is not available for eight of the participants | Number | participants |
| ||||||||||||||||||||||
| Use of Photons for <20% radiation dose | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Incidence of Ototoxicity | Percentage participants who experienced ototoxicity as measured by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 after the completion of radiation therapy in the overall participant population and by baseline measure subgroups. Incidence is shown after follow-up of 3 years, 5 years, 7 years, and 10 years. | The overall study population after the stated durations of follow-up. Follow-up is ongoing and data is not yet available for the 10 year time point. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 Years, 5 years, 7 years, 10 years |
|
|
| |||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 3 years of follow-up (as determined by CTCAE 3.0). Incidence is grouped by hormone type and risk group | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 5 years of follow-up (as determined by CTCAE 3.0). Incidence is shown by hormone type and risk group. | Posted | Number | 95% Confidence Interval | percentage of participants | 5 years |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 7 years of follow-up, as determined by CTCAE 3.0. Incidence is shown by hormone type and risk group | Posted | Number | 95% Confidence Interval | percentage of participants | 7 years |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) as determined by CTCAE 3.0) at year 3, year 5, and year 7 of follow-up. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years, 5 years, 7 years |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Mean Change Per-Year in Neurocognitive Outcomes | The mean change per-year in neurocognitive outcomes as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full Scale Intelligence Quotient (FSIQ) of children with the use of four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale that has an average score of 100 and standard deviation of 15 points in the general population, meaning on average 68% of test takers would be within +/- 15 points of 100 and 95% within +/- 30 points. Higher scores represent higher intelligence and lower score represent reduced intelligence. Participants were assessed for changes in score with the use of repeated testing during a median follow-up time of 5.2 years. Repeated measures were taken at baseline, 1, 3, 5, and 7 years or until the participant was not available for evaluation (whichever comes first). | The study participants that were evaluated for changes in neurocognitive outcomes | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline, 1, 3, 5, 7 years |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Progression Free Survival | The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group. | Follow-up is ongoing and data is not yet available for the 10 year follow-up time point. | Posted | Number | 95% Confidence Interval | percentage of participants surviving | 5 years, 7 years, 10 years |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | the percentage of participants surviving after five and seven years and at the end of follow-up in the overall population. Survival is shown by risk and histological group. | Follow-up for the 10 year follow-up is still ongoing and the data is not yet available. | Posted | Number | 95% Confidence Interval | percentage of participants surviving | 5 years, 7 years, 10 years |
|
|
Through study completion, median duration of 7 years
Acute toxicity is assessed weekly during craniospinal irradiation (CSI) treatment and late side effects/complications are assessed during routine clinic visits starting at 90 days after the completion of radiation therapy. Participants were assessed for toxicity for the duration of followup, meaning until the patient withdraws from the study, is taken off the protocol, or dies.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Radiation Therapy | radiation therapy: Radiation therapy with proton beam to standard doses | 13 | 59 | 13 | 59 | 59 | 59 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Stroke | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| esophhagitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Radiation dermatitis (scalp or back) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Weight Loss | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cataracts | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Obesity | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| CNS brainstem injury | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Scoliosis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Truncal muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nystagmus | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nancy Tarbell, Pediatric Radiation Oncologist | Massachusetts General Hospital | 617-724-1836 | NTARBELL@mgh.harvard.edu |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
| Anaplastic or Large Cell Variant |
|
| High |
|
| Yes : ACNS0334 |
|
| Yes : A9961 |
|
| No |
|
| Standard Risk |
|
|
| Intermediate-high risk |
|
|
| Male |
|
|
| Female |
|
|
| <8 years old |
|
|
| ≥8 years old |
|
|
| Vetriculoperitoneal shunt |
|
|
| No vetriculoperitoneal shunt |
|
|
| Cisplatin total dose ≤300 mg/m2 |
|
|
| Cisplatin total dose >300 mg/m2 |
|
|
|
|
|
|
|
|
|
|