Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma


About this study

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. Patients will be more likely to be randomized to proton beam radiation therapy. 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Tumor tissue must be available for submission for central pathology review
  • 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
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 60 days prior to registration
    • Imaging of the brain within 60 days prior to registration
  • Only English speaking patients are eligible to participate as the cognitive and quality of life assessments are available only in English
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Karnofsky performance status of >= 70 within 60 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)
  • Bilirubin =< 1.5 upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • CD4 lymphocyte count is highly encouraged
  • Women of childbearing age must have a negative serum pregnancy test within 14 days prior to registration
  • Post-operative magnetic resonance (MR) imaging must be obtained for radiation therapy planning; enrolling sites are highly encouraged to obtain thin-slice volumetric fluid attenuated inversion recovery (FLAIR) and T1 post contrast sequences for planning purposes
  • The following baseline neurocognitive assessments must be completed and uploaded within 27 calendar days prior to step 2 registration: HVLT-R, TMT, and COWA
    • NOTE: Completed baseline neurocognitive assessments can be uploaded at the time of step 1 registration
  • The following baseline patient reported outcome assessments must be completed and uploaded within 27 calendar days prior to Step 2 registration: MDASI-BT, LASA QOL, WPAI
  • Financial clearance for proton therapy treatment within 30 days following step 1 registration
  • Centrally reviewed histologically proven diagnosis of supratentorial, Word Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma; tissue must be submitted x calendar days after step 1 registration
  • Documentation must be uploaded within 15 business days and will be verified by the translational/pathology study co-chairs within 5 business days after receiving the upload; the documentation should demonstrate 1) evaluation of known IDH1 and IDH2 mutational hotspots (sequencing is encouraged) evaluation of chromosomes 1p and 19q copy number utilizing either fluorescence in situ hybridization (FISH) or other suitable assay

Exclusion Criteria:

  • Definitive clinical or radiologic evidence of metastatic disease; if applicable
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity or cervix are permissible)
  • Prior cranial radiotherapy or radiotherapy to the head and neck where potential field overlaps would exist
  • Prior chemotherapy or radiotherapy for any brain tumor
  • Histologic diagnosis of glioblastoma (WHO grade IV) or pilocytic astrocytoma (WHO grade I)
  • Definitive evidence of multifocal disease
  • Planned use of cytotoxic chemotherapy during radiation (only adjuvant temozolomide therapy will be used on this protocol)
  • Patients with infra-tentorial tumors are not eligible
  • Prior history of neurologic or psychiatric disease believed to impact cognitive function
  • The use of memantine during or following radiation is NOT allowed
  • Severe, active co-morbidity defined as follows:
    • Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment
    • Transmural myocardial infarction within the last 6 months prior to step 2 registration; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 28 days prior to step 2 registration (Note: EKG to be performed only if clinical suspicion of cardiac issue)
    • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
    • Serious and inadequately controlled arrhythmia at step 2 registration
    • Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for surgical resection
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
    • Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol
    • Any other severe immunocompromised condition
    • Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
    • End-stage renal disease (i.e., on dialysis or dialysis has been recommended)
    • Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy
  • Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction); note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Anita Mahajan, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions