Glioma Clinical Trial
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
Verified date | March 2024 |
Source | NRG Oncology |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 148 |
Est. completion date | January 2030 |
Est. primary completion date | June 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Prior to STEP 1 REGISTRATION - 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 - 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 30 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 - BUN < 30 mg/dl - Serum creatinine < 1.5 mg/dl - Post-operative magnetic resonance (MR) imaging with contrast is mandatory obtained for radiation therapy planning; enrolling sites are highly encouraged to obtain thin-slice (<1.5 mm) 3D T1 pre and post contrast and Axial T2/FLAIR sequences for planning purposes - Prior to STEP 2 REGISTRATION - The following baseline neurocognitive assessments must be completed and uploaded prior to step 2 registration: HVLT-R, TMT Parts A and B, and COWA - 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 to step 2 registration - Centrally reviewed histologically proven diagnosis of supratentorial, Word Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma, with IDH mutation 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 |
Country | Name | City | State |
---|---|---|---|
United States | Emory Proton Therapy Center | Atlanta | Georgia |
United States | Emory University Hospital Midtown | Atlanta | Georgia |
United States | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia |
United States | Maryland Proton Treatment Center | Baltimore | Maryland |
United States | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland |
United States | UM Upper Chesapeake Medical Center | Bel Air | Maryland |
United States | University of Alabama at Birmingham Cancer Center | Birmingham | Alabama |
United States | Boca Raton Regional Hospital | Boca Raton | Florida |
United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
United States | Northwestern University | Chicago | Illinois |
United States | Case Western Reserve University | Cleveland | Ohio |
United States | Central Maryland Radiation Oncology in Howard County | Columbia | Maryland |
United States | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois |
United States | UM Baltimore Washington Medical Center/Tate Cancer Center | Glen Burnie | Maryland |
United States | M D Anderson Cancer Center | Houston | Texas |
United States | University of Kansas Cancer Center | Kansas City | Kansas |
United States | University of Kansas Cancer Center - North | Kansas City | Missouri |
United States | University of Kansas Cancer Center - Lee's Summit | Lee's Summit | Missouri |
United States | Miami Cancer Institute | Miami | Florida |
United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York |
United States | University of Kansas Cancer Center at North Kansas City Hospital | North Kansas City | Missouri |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | University of Kansas Cancer Center-Overland Park | Overland Park | Kansas |
United States | University Hospitals Parma Medical Center | Parma | Ohio |
United States | University of Pennsylvania/Abramson Cancer Center | Philadelphia | Pennsylvania |
United States | University Hospitals Portage Medical Center | Ravenna | Ohio |
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Maine Medical Center- Scarborough Campus | Scarborough | Maine |
United States | FHCC at Northwest Hospital | Seattle | Washington |
United States | University of Washington Medical Center - Montlake | Seattle | Washington |
United States | Mercy Hospital Springfield | Springfield | Missouri |
United States | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois |
United States | University of Kansas Hospital-Westwood Cancer Center | Westwood | Kansas |
Lead Sponsor | Collaborator |
---|---|
NRG Oncology | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Assessment of dose-response relationships | The dose-response relationship between cognition, using the CTB COMP and each individual test score, and neuro-anatomic dosimetry, including the hippocampus and whole brain, will be assessed. The decline, as calculated using the Reliable Change Index, will be used to determine neurocognitive impairment. The dose-response curve will be modeled using a non-linear model. | Up to 10 years | |
Other | Assessment of tumor molecular status | Cognition, using the CTB COMP and each individual test score, will be compared by 1p19q status. A general linear model using maximum likelihood estimation will be built for CTB COMP and each individual test score over time including baseline test score, 1p19q status, treatment arm, and stratification factors. | Up to 10 years | |
Primary | Change in cognition as measured by the 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 | Baseline to up to 10 years | |
Secondary | Change in quality of life as measured by the LASA scale | The change from baseline to each follow-up time point (calculated as baseline score subtracted from follow-up score) will be compared between treatment arms using a t-test, or Wilcoxon test if the data is not normally distributed. A one-sided alpha=0.05 will be used for the LASA. A general linear model with maximum likelihood estimation will be used to assess symptom and QOL trends across time. | Up to 10 years | |
Secondary | Change in symptoms as measured by MDASI-BT | The change from baseline to each follow-up time point (calculated as baseline score subtracted from follow-up score) will be compared between treatment arms using a t-test, or Wilcoxon test if the data is not normally distributed. A reduced one-sided significance level will be used for the multiple comparisons in the MDASI-BT using the Bonferroni adjustment (alpha=0.017 for disease related factors and alpha=0.025 for treatment related symptoms and overall impact). A general linear model with maximum likelihood estimation will be used to assess symptom trends across time. | Baseline to up to 10 years | |
Secondary | Cognition as measured by COWA | The COWA will be analyzed using a general linear model with maximum likelihood estimation. Standardized scores will be used. | Up to 10 years | |
Secondary | Cognition as measured by TMT parts A and B | The TMT parts A & B will be analyzed using a general linear model with maximum likelihood estimation. Standardized scores will be used. | Up to 10 years | |
Secondary | Cognition as measured by HVLT-R | The HVLT-R will be analyzed using a general linear model with maximum likelihood estimation. Standardized scores will be used. | Up to 10 years | |
Secondary | Incidence of adverse events (AEs) graded according to the National Cancer Institute's Common Terminology for Adverse Events version 4.0 | Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. Grade 3+ treatment related AEs will be compared between arms using a chi-square test, or Fisher's exact test if cell frequencies are < 5, at the one-sided 0.05 significance level. | Up to 10 years | |
Secondary | Local control as assessed by RANO criteria | Local control will be estimated using cumulative incidence, treating death prior to an event as a competing risk. Gray's test will be used to compare local control rates between arms. Cause-specific Cox proportional hazards models will be used for local control, adjusting for treatment arm and stratification factors. A two-sided significance level of 0.05 will be used for comparisons between arms. | Up to 10 years | |
Secondary | Overall survival (OS) | OS will be estimated using the Kaplan-Meier method and compared between arms using the log rank test. Cox proportional hazards models will be used for OS adjusting for treatment arm and stratification factors. | From randomization to the date of death, assessed up to 10 years | |
Secondary | Progression-free survival (PFS) | A confidence interval will be used to determine if the PFS rate in the proton arm is greater than that in the photon at 1 year. PFS will be estimated using the Kaplan-Meier method and compared between arms using the log rank test. Cox proportional hazards models will be used for PFS adjusting for treatment arm and stratification factors. | From date of randomization to date of progression or death, whichever occurs first, assessed up to 10 years |
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