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

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00105560
• Other study ID #: CDR0000415841
• Secondary ID: P01CA021239MGH-9
• Status: Completed
• Phase: N/A
• Start date: May 2002
• Est. completion date: December 2020

Study information

• Verified date: December 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: December 2020
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Long-term Effects Secondary to Cancer Therapy in Children
• Medulloblastoma
• Nervous System Neoplasms
• Pinealoma

Intervention

Radiation:
• radiation therapy
Radiation therapy with proton beam to standard doses

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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	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.	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	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.	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).	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.	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.	5 years, 7 years, 10 years