Clinical trial NCT00105560: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-03-16
Enrollment: 59
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cumulative Incidence of Ototoxicity
timeFrame: 3 Years, 5 years, 7 years, 10 years
Secondary outcomes:
measure: Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years
timeFrame: 3 years
measure: Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years
timeFrame: 5 years
measure: Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
timeFrame: 7 years
measure: Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
timeFrame: 3 years, 5 years, 7 years
measure: Mean Change Per-Year in Neurocognitive Outcomes
timeFrame: Baseline, 1, 3, 5, 7 years
measure: Progression Free Survival
timeFrame: 5 years, 7 years, 10 years
measure: Overall Survival
timeFrame: 5 years, 7 years, 10 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Nancy J. Tarbell, MD
role: STUDY_CHAIR
References:
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.
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.