Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients with IDH Mutant Grade II or III Glioma
Brain & Spinal Cord Tumor
18 Years and older, Male and Female
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.
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.
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.
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.
- PRIOR TO STEP 1 REGISTRATION
- Tumor tissue must be available for submission for central pathology review
- Grade II and III gliomas IDH mutant gliomas including; diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma
- Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories and be uploaded prior to Step 2 registration
- Age >= 18
- The trial is open to both genders
- Only English or French speaking patients are eligible to participate as the cognitive assessments are only available in these languages
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- History and physical exam, and Karnofsky performance status of >= 70 within 30 days prior to registration
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 60 days prior to registration)
- Platelets >= 100,000 cells/mm^3 (within 60 days prior to registration)
- Hemoglobin >= 10.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (within 60 days prior to registration)
- Bilirubin =< 1.5 upper limit of normal (ULN) (within 60 days prior to registration)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 60 days prior to registration)
- Blood urea nitrogen (BUN) < 30 mg/dl (within 60 days prior to registration)
- Serum creatinine < 1.5 mg/dl (within 60 days prior to registration)
- Pre-operative MRI imaging of the brain available for radiation planning
- Post-operative MRI imaging with contrast is mandatory obtained for radiation therapy planning; enrolling sites are not mandated although highly encouraged to obtain thin-slice (< 1.5 mm) 3 dimensional (D) pre and post contrast and axial T2/FLAIR sequences for planning purposes
- Patients must be able to swallow capsules
- PRIOR TO STEP 2 REGISTRATION
- Histologically proven diagnosis of supratentorial, World Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma, with IDH mutation confirmed by central review
- The following baseline neurocognitive assessments must be completed and uploaded prior to Step 2 registration: HVLT-R (recall, delayed recall, and recognition), TMT Parts A and B, and COWA; the neurocognitive assessment will be uploaded into a folder in the NRG Medidata RAVE System for central evaluation; once the upload and scoring of the tools are complete, a notification will be sent within 3 business days to the Research Associate (RA) to proceed to Step 2; in order for the patient to be eligible, at least 5 of the 6 neurocognitive assessments must be able to be scored (i.e. free of any errors)
- Completion of all items on the following baseline quality of life forms: MDASI-BT, LASA QOL, WPAI-GH and Employment Questionnaire; these quality of life forms will be required and data entered at step 2 registration
- Financial clearance for proton therapy treatment prior step 2 registration
- Women of childbearing age must have a negative serum pregnancy test within 14 days prior to step 2 registration
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials