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Radiation Therapy in Treating Young Patients With Gliomas

A Phase II Study of Conformal Radiotherapy In Patients With Low-Grade Gliomas

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00238264
Enrollment
92
Registered
2005-10-13
Start date
2006-11-30
Completion date
2018-12-31
Last updated
2019-08-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Brain Tumor, Central Nervous System Tumor

Keywords

childhood oligodendroglioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, childhood low-grade cerebral astrocytoma, recurrent childhood visual pathway and hypothalamic glioma, untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma

Brief summary

RATIONALE: Specialized radiation therapy that delivers radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well radiation therapy works in treating young patients with gliomas.

Detailed description

OBJECTIVES: Primary * Determine the marginal-failure rate in young patients with low-grade gliomas treated with reduced-field conformal radiotherapy. Secondary * Determine the progression-free survival, event-free survival, and overall survival rates of young patients treated with this regimen. * Determine quality of life of patients treated with this regimen. * Correlate MIB-1 labeling index with progression-free survival and overall survival of these patients. OUTLINE: This is a multicenter study. Patients undergo reduced-field conformal radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline or 6 weeks after completion of study treatment and then at 2 and 5 years (closed as of 10/27/2010). After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Interventions

RADIATIONradiation therapy

Undergo 3D-CRT Undergo proton radiation therapy Undergo IMRT

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Children's Oncology Group
Lead SponsorNETWORK

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
3 Years to 20 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed\* low-grade glioma, including any of the following: * Juvenile pilocytic astrocytoma (JPA) or pleomorphic JPA * Diffuse astrocytoma, including any of the following subtypes: * Fibrillary astrocytoma * Gemistocytic astrocytoma * Subependymal giant cell astrocytoma * Pleomorphic xanthoastrocytoma * Low-grade oligoastrocytoma * Low-grade oligodendroglioma * Low-grade glioma not otherwise specified NOTE: \*Patients with chiasmatic lesions who have contiguous extension of tumor into other regions of the visual pathway by CT scan or MRI are eligible without histopathologic confirmation; repeat biopsy required for patients with recurrent tumors that enhance but whose initial tumor did not * Measurable disease by radiography * Meets any of the following criteria: * Progressive nonresectable disease * Any location in the brain * Patients with a less than gross total resection are eligible provided they are symptomatic from their tumor OR the risk from neurologic impairment with progression is high enough to warrant immediate treatment * Has undergone biopsy only * Must have received ≥ 1 course of prior chemotherapy (for patients \< 10 years of age) * Prior chemotherapy optional (for patients ≥ 10 years of age) * No type-1 neurofibromatosis * No evidence of leptomeningeal dissemination PATIENT CHARACTERISTICS: Age * 3 to 20 Performance status * ECOG 0-2 OR * Karnofsky 50-100% (for patients \> 16 years of age) OR * Lansky 50-100% (for patients ≤ 16 years of age) Life expectancy * At least 1 year Hematopoietic * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 (transfusion independent) * Hemoglobin ≥ 10.0 g/dL (transfusions allowed) Hepatic * Not specified Renal * Not specified Other * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * Not in status epilepticus, coma, or requiring assisted ventilation prior to study entry * Patients with a seizure disorder are eligible provided they are on anticonvulsants AND disease is well controlled PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * Recovered from prior chemotherapy * No concurrent chemotherapy Endocrine therapy * Concurrent dexamethasone allowed provided patient has been on a stable dose for ≥ 2 weeks prior to study entry * Concurrent dexamethasone allowed for symptoms of increased intracranial pressure Radiotherapy * No prior radiotherapy Surgery * See Disease Characteristics Other * No other concurrent anticancer therapy

Design outcomes

Primary

MeasureTime frameDescription
Marginal-failure RateUp to 5 yearsPatients who do not recur as well as those with either central or distant recurrence would be treatment successes for this endpoint. Monitoring will be based on a Bayesian rule, with binomial likelihood and a Beta on the parameter p, the proportion of failures that are marginal failures.

Secondary

MeasureTime frameDescription
Event-free Survival Probability3 yearsTo estimate the event-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation
Overall Survival Probability3 yearsTo estimate the overall survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.
Progression-free Survival Probability3 yearsTo estimate the progression-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.
MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established MethodsAt baselineThe MIB-1 labeling Index will be calculated as the percentage of tumor nuclei that are immunoreactive.
Correlation MIB-1 Labeling Index With PFSUp to 10 yearsThe primary methods of analysis will be via stratified Cox regression
Quality of Life (QOL)Up to 5 yearsQOL accessed using the Behavior Assessment System for Children (BASC), the Adaptive Behavior Assessment System (ABAS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Symptom Checklist-90-R (SCL-90-R).

Countries

Australia, Canada, New Zealand, Puerto Rico, Switzerland, United States

Participant flow

Participants by arm

ArmCount
Reduced-field Conformal Radiation Therapy
Patients undergo reduced-field conformal radiation therapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. radiation therapy: Undergo 3D-CRT Undergo proton radiation therapy Undergo IMRT
92
Total92

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDeath7
Overall StudyIneligible7
Overall StudyLost to Follow-up18
Overall StudyWithdrawal by Subject4

Baseline characteristics

CharacteristicReduced-field Conformal Radiation Therapy
Age, Categorical
<=18 years
86 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
6 Participants
Age, Continuous13.6 Years
Ethnicity (NIH/OMB)
Hispanic or Latino
9 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
82 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
2 Participants
Race (NIH/OMB)
Black or African American
9 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
6 Participants
Race (NIH/OMB)
White
75 Participants
Sex: Female, Male
Female
49 Participants
Sex: Female, Male
Male
43 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
5 / 85
serious
Total, serious adverse events
5 / 85

Outcome results

Primary

Marginal-failure Rate

Patients who do not recur as well as those with either central or distant recurrence would be treatment successes for this endpoint. Monitoring will be based on a Bayesian rule, with binomial likelihood and a Beta on the parameter p, the proportion of failures that are marginal failures.

Time frame: Up to 5 years

Population: All evaluable patients were included in this analysis (n = 84). One eligible patient was deemed to be not evaluable due to progression during treatment, and was excluded from the analysis per protocol.

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyMarginal-failure Rate0 percentage of failure rate
Secondary

Correlation MIB-1 Labeling Index With PFS

The primary methods of analysis will be via stratified Cox regression

Time frame: Up to 10 years

Population: All eligible patients with MIB-1 data available were included in this analysis. Per protocol, patients were stratified by age and tumor location. Based on a predefined cutoff, patients were categorized as MIB high or low (high: \>= 2; low: \< 2). The hazard ratio below is for patients with MIB high (low is the reference level).

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyCorrelation MIB-1 Labeling Index With PFS1.08 Hazard ratio
Secondary

Event-free Survival Probability

To estimate the event-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation

Time frame: 3 years

Population: All eligible patients were included in the analysis, per protocol.

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyEvent-free Survival Probability77.1 Percentage 3-year EFS rate
Secondary

MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods

The MIB-1 labeling Index will be calculated as the percentage of tumor nuclei that are immunoreactive.

Time frame: At baseline

Population: All eligible patients with MIB-1 labeling index available.

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyMIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods3.1 percentage of tumor nuclei
Secondary

Overall Survival Probability

To estimate the overall survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.

Time frame: 3 years

Population: All eligible patients were included in the analysis, per protocol.

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyOverall Survival Probability94.0 Percentage 3-year OS rate
Secondary

Progression-free Survival Probability

To estimate the progression-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.

Time frame: 3 years

Population: All eligible patients were included in the analysis, per protocol.

ArmMeasureValue (NUMBER)
Reduced-field Conformal Radiation TherapyProgression-free Survival Probability77.1 Percentage 3-year PFS rate
Secondary

Quality of Life (QOL)

QOL accessed using the Behavior Assessment System for Children (BASC), the Adaptive Behavior Assessment System (ABAS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Symptom Checklist-90-R (SCL-90-R).

Time frame: Up to 5 years

Population: The QOL assessments were removed from the protocol as part of Amendment #1A (as of 10/27/2010) due to extremely low compliance. No QOL data were available for statistical analysis.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026