Ignite Creation Date:
2025-12-25 @ 3:38 AM
Ignite Modification Date:
2026-01-08 @ 8:30 AM
Study NCT ID:
NCT03180502
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-11
First Post:
2017-06-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma
Sponsor:
NRG Oncology
Organization:
Study Overview
Official Title:
A Phase II Randomized Trial of Proton Vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients With IDH Mutant, Low to Intermediate Grade Gliomas
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase II clinical trial studies the side effects and how well proton beam or intensity-modulated radiation therapy works in preserving brain function in patients with IDH mutant grade II or III glioma. Proton beam radiation therapy uses tiny charged particles to deliver radiation directly to the tumor and may cause less damage to normal tissue. Intensity-modulated or photon beam radiation therapy uses high-energy x-ray beams shaped to treat the tumor and may also cause less damage to normal tissue. It is not yet known if proton beam radiation therapy is more effective than photon-based beam intensity-modulated radiation therapy in treating patients with glioma.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine whether proton therapy, compared to intensity-modulated radiation therapy (IMRT), preserves cognitive outcomes over time as measured by the Clinical Trial Battery Composite (CTB COMP) score (calculated from the Hopkins Verbal Learning Test Revised \[HVLT-R\]) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Controlled Oral Word Association (COWA) test, Trail Making Test (TMT) part A and part B.
SECONDARY OBJECTIVES:
I. To assess whether treatment with proton therapy preserves neurocognitive function as measured separately by each test, HVLT-R, TMT parts A \& B, and COWA.
II. To document and compare treatment related symptoms, overall symptom impact, and disease related factor groupings, utilizing the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT), for both treatment arms.
III. To assess whether treatment with proton therapy, compared to IMRT, results in superior quality of life as measured by the Linear Analog Scale Assessment (LASA) scale.
IV. To compare local control patterns of failure and overall and progression-free survival between the two treatment arms.
V. To assess adverse events. VI. To compare Illumnia MethylationEPIC beadchip array-derived IDH and 1p19q status determined centrally to that submitted by enrolling sites.
TERTIARY OBJECTIVES:
I. To assess the impact of chemotherapy use on cognitive outcomes, symptom outcomes and quality of life.
II. To assess dose-response relationships between neuro-anatomic dosimetry and cognitive outcomes within and between treatment arms.
III. To evaluate the association between tumor molecular status and cognition at baseline and within and between treatment arms over time.
IV. To assess patterns of failure and pseudo progression as a function of radiation delivery type and dose received.
V. To assess local control, overall survival and, progression free survival in IDH mutant grade II and III tumors.
VI. To collect blood samples for future studies seeking to correlate changes in peripheral blood biomarkers (genes, micro ribonucleic acid \[RNA\], proteins, lymphocyte count, melatonin, etc) and the study endpoints.
VII. To document and compare the impact of low to intermediate gliomas and therapy on patients' work and activity participation (The Work Productivity and Activity Impairment \[WPAI:GH\] Questionnaire: General Health version 2.0) as well as the relationship between changes in patients' work and activity participation and neurocognitive function and patient reported symptoms and interference.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo photon-based IMRT once daily (QD), 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.
ARM II: Patients undergo proton beam radiation therapy QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo MRI and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 6 and 12 months and then yearly for 10 years.
I. To determine whether proton therapy, compared to intensity-modulated radiation therapy (IMRT), preserves cognitive outcomes over time as measured by the Clinical Trial Battery Composite (CTB COMP) score (calculated from the Hopkins Verbal Learning Test Revised \[HVLT-R\]) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Controlled Oral Word Association (COWA) test, Trail Making Test (TMT) part A and part B.
SECONDARY OBJECTIVES:
I. To assess whether treatment with proton therapy preserves neurocognitive function as measured separately by each test, HVLT-R, TMT parts A \& B, and COWA.
II. To document and compare treatment related symptoms, overall symptom impact, and disease related factor groupings, utilizing the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT), for both treatment arms.
III. To assess whether treatment with proton therapy, compared to IMRT, results in superior quality of life as measured by the Linear Analog Scale Assessment (LASA) scale.
IV. To compare local control patterns of failure and overall and progression-free survival between the two treatment arms.
V. To assess adverse events. VI. To compare Illumnia MethylationEPIC beadchip array-derived IDH and 1p19q status determined centrally to that submitted by enrolling sites.
TERTIARY OBJECTIVES:
I. To assess the impact of chemotherapy use on cognitive outcomes, symptom outcomes and quality of life.
II. To assess dose-response relationships between neuro-anatomic dosimetry and cognitive outcomes within and between treatment arms.
III. To evaluate the association between tumor molecular status and cognition at baseline and within and between treatment arms over time.
IV. To assess patterns of failure and pseudo progression as a function of radiation delivery type and dose received.
V. To assess local control, overall survival and, progression free survival in IDH mutant grade II and III tumors.
VI. To collect blood samples for future studies seeking to correlate changes in peripheral blood biomarkers (genes, micro ribonucleic acid \[RNA\], proteins, lymphocyte count, melatonin, etc) and the study endpoints.
VII. To document and compare the impact of low to intermediate gliomas and therapy on patients' work and activity participation (The Work Productivity and Activity Impairment \[WPAI:GH\] Questionnaire: General Health version 2.0) as well as the relationship between changes in patients' work and activity participation and neurocognitive function and patient reported symptoms and interference.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo photon-based IMRT once daily (QD), 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.
ARM II: Patients undergo proton beam radiation therapy QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 28 days after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity. Patients undergo MRI and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 6 and 12 months and then yearly for 10 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: