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

NCT03180502 | Active Not Recruiting Phase 2

• 3 other identifiers: NRG-BN005NCI-2017-00203U10CA180868
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 34

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.

Conditions

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Diffuse Astrocytoma; Glioma; Oligoastrocytoma; Oligodendroglioma; WHO Grade 3 Glioma

Outcome Measures

Primary Outcomes (1)

• Change in cognition as measured by the Clinical Trial Battery Composite (CTB COMP) score

  Assessed with a general linear model with maximum likelihood estimation. Three models will be conducted. Baseline CTB COMP score, treatment arm, time, treatment by time interaction (if significant) and stratification factors will be included in the model for the primary endpoint. A second model will be built with these same variables and relevant covariates, such as total volume of intracranial disease, gross tumor volume (GTV) and clinical tumor volume (CTV) size, histology, anti-epileptic use, and disease response to therapy (as measured by Response Assessment in Neuro-Oncology \[RANO\] criteria). Other than baseline score CTB COMP, treatment arm, and time, only covariates with a p-value \< 0.10 will be retained in the model. A third model will be conducted at 10 years using the additional time points of neurocognitive assessments.

  Baseline to up to 10 years

Secondary Outcomes (8)

• Cognition as measured individually by Hopkins Verbal Learning Test Revised (HVLT-R), Trail Making Test (TMT) parts A and B, and Controlled Oral Word Association (COWA)

  Up to 10 years

• Change in symptoms as measured by M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT)

  Baseline to up to 10 years

• Change in quality of life as measured by the Linear Analog Scale Assessment (LASA) scale

  Up to 10 years

• Overall survival (OS)

  From randomization to the date of death, assessed up to 10 years

• Local control as assessed by Response Assessment in Neuro-Oncology (RANO) criteria

  Up to 10 years

Other Outcomes (5)

• Impact of chemotherapy use on cognition assessed by Clinical Trial Battery Composite (CTB COMP) and each individual test score

  Up to 10 years

• Assessment of dose-response relationships

  Up to 10 years

• Assessment of tumor molecular status

  Up to 10 years

Study Arms (2)

Arm I (photon-based IMRT, temozolomide)

ACTIVE COMPARATOR

Patients undergo photon-based IMRT 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.

Procedure: Biospecimen Collection; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Temozolomide

Arm II (proton beam radiation therapy, temozolomide)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Temozolomide

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Arm I (photon-based IMRT, temozolomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Proton Beam Radiation Therapy RADIATION

Undergo proton beam radiation therapy

Also known as: External beam radiation therapy protons (procedure), External Beam Radiotherapy (protons), PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy, Proton Radiation Therapy, PROTON Therapy, Radiation, Proton Beam

Arm II (proton beam radiation therapy, temozolomide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Questionnaire Administration OTHER

Ancillary studies

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Temozolomide DRUG

Drug

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Arm I (photon-based IMRT, temozolomide); Arm II (proton beam radiation therapy, temozolomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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 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 registration
• Serious and inadequately controlled arrhythmia at step 2 registration

Sponsors & Collaborators

• NRG Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (34)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Emory Proton Therapy Center

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

Location

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

MaineHealth Maine Medical Center- Scarborough

Scarborough, Maine, 04074, United States

Location

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

UM Upper Chesapeake Medical Center

Bel Air, Maryland, 21014, United States

Location

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, 21044, United States

Location

UM Baltimore Washington Medical Center/Tate Cancer Center

Glen Burnie, Maryland, 21061, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University Hospitals Parma Medical Center

Parma, Ohio, 44129, United States

Location

University Hospitals Portage Medical Center

Ravenna, Ohio, 44266, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

FHCC at Northwest Hospital

Seattle, Washington, 98133, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioma

Interventions

Specimen Handling; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; Proton Therapy; Protons; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Heavy Ion Radiotherapy; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David R Grosshans

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: June 8, 2017
• Study Start: January 23, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (34)