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Proton Beam Radiation Therapy in Treating Young Patients Who Have Undergone Biopsy or Surgery for Medulloblastoma or Pineoblastoma

Primary Purpose

Brain and Central Nervous System Tumors, Long-term Effects Secondary to Cancer Therapy in Children

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
radiation therapy
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring long-term effects secondary to cancer therapy in children, untreated childhood medulloblastoma, untreated childhood pineoblastoma

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed medulloblastoma or pineoblastoma Standard-risk or high-risk disease Must have undergone biopsy or attempted surgical resection of the tumor within the past 35 days Requires craniospinal irradiation PATIENT CHARACTERISTICS: Age 3 to 21 Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No more than 1 prior chemotherapy regimen No prior IV or intrathecal methotrexate No prior intrathecal thiotepa Concurrent cisplatin-based chemotherapy, including chemotherapy administered on another study, allowed Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radiation therapy

Arm Description

This is a single arm study of radiation therapy with protons to standard doses.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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
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.
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).
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.
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.

Full Information

First Posted
March 15, 2005
Last Updated
December 3, 2021
Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00105560
Brief Title
Proton Beam Radiation Therapy in Treating Young Patients Who Have Undergone Biopsy or Surgery for Medulloblastoma or Pineoblastoma
Official Title
Phase II Study of Craniospinal and Posterior Fossa Irradiation Using Proton Beam Radiotherapy for Medulloblastoma and Pineoblastoma: Assessment of Acute and Long Term Sequelae
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
May 2002 (Actual)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
OBJECTIVES: Determine the 3-year incidence and severity of ototoxicity in young patients with medulloblastoma or pineoblastoma treated with adjuvant proton beam craniospinal and posterior fossa radiotherapy. Determine the incidence of primary hypothyroidism and other endocrine dysfunction (neuroendocrine and end organ) in patients treated with this regimen. Determine the incidence and severity of neurocognitive abnormalities in patients treated with this regimen. Determine the acute side effects of this regimen, including esophagitis, upper and lower gastrointestinal tract disease, and weight loss, in these patients. Determine the 3-year progression-free survival rate of patients treated with this regimen. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Long-term Effects Secondary to Cancer Therapy in Children
Keywords
long-term effects secondary to cancer therapy in children, untreated childhood medulloblastoma, untreated childhood pineoblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Radiation therapy
Arm Type
Experimental
Arm Description
This is a single arm study of radiation therapy with protons to standard doses.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
Radiation therapy with proton beam to standard doses
Primary Outcome Measure Information:
Title
Cumulative Incidence of Ototoxicity
Description
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.
Time Frame
3 Years, 5 years, 7 years, 10 years
Secondary Outcome Measure Information:
Title
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years
Description
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
Time Frame
3 years
Title
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years
Description
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.
Time Frame
5 years
Title
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
Description
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
Time Frame
7 years
Title
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
Description
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.
Time Frame
3 years, 5 years, 7 years
Title
Mean Change Per-Year in Neurocognitive Outcomes
Description
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).
Time Frame
Baseline, 1, 3, 5, 7 years
Title
Progression Free Survival
Description
The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group.
Time Frame
5 years, 7 years, 10 years
Title
Overall Survival
Description
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.
Time Frame
5 years, 7 years, 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed medulloblastoma or pineoblastoma Standard-risk or high-risk disease Must have undergone biopsy or attempted surgical resection of the tumor within the past 35 days Requires craniospinal irradiation PATIENT CHARACTERISTICS: Age 3 to 21 Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No more than 1 prior chemotherapy regimen No prior IV or intrathecal methotrexate No prior intrathecal thiotepa Concurrent cisplatin-based chemotherapy, including chemotherapy administered on another study, allowed Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy J. Tarbell, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26830377
Citation
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. Erratum In: Lancet Oncol. 2020 Mar;21(3):e132.
Results Reference
result
PubMed Identifier
30118397
Citation
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.
Results Reference
derived

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Proton Beam Radiation Therapy in Treating Young Patients Who Have Undergone Biopsy or Surgery for Medulloblastoma or Pineoblastoma

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