Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine®) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma
Glioblastoma, Gliosarcoma
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)
- STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the NYU Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 23. If tissue cannot be received by postoperative calendar day 23, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 6 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be conveyed to NRG Oncology within 10 business days of receipt of tissue. Note: In the event of an additional tumor resection(s), tissue must be received within 23 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis
STEP 1 REGISTRATION: Contrast-enhanced brain MRI within 4 days after surgery
- Magnetic resonance imaging (MRI) with Axial T2 weighted FLAIR{preferred} or T2 TSE/FSE and 3D contrast-enhanced T1 sequences are required.
- 3-dimensional (3D) pre contrast-enhanced T1 sequences are strongly suggested
- STEP 1 REGISTRATION: Willing to use highly effective method of contraception for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 6 months after completing treatment; this inclusion is necessary because the treatment in this study may be significantly teratogenic
- STEP 1 REGISTRATION: The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
- STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
- STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology review (See Section 10 for details). Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded. Patients with unmethylated MGMT may be considered for enrollment on NRG-BN007
- STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at Step 2.)
- STEP 2 REGISTRATION: History/physical examination within 28 days prior to Step 2 registration
- STEP 2 REGISTRATION: Karnofsky performance status (KPS) >= 70 within 28 days prior to Step 2 registration
- STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to Step 2 registration
- STEP 2 REGISTRATION: Age 18-70 years
- STEP 2 REGISTRATION: Hemoglobin >= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
- STEP 2 REGISTRATION: Leukocytes >= 2,000/mm^3
- STEP 2 REGISTRATION: Absolute neutrophil count >= 1,500/mm^3
- STEP 2 REGISTRATION: Platelets >= 100,000/mm^3
- STEP 2 REGISTRATION: Total bilirubin =< 1.5 x institutional/lab upper limit of normal (ULN)
- STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
- STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
- STEP 2 REGISTRATION: Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula
STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
STEP 2 REGISTRATION: For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid [RNA]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
- STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to step 2 registration are eligible for this trial. Testing is not required for entry into protocol
STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of childbearing potential) within 7 days prior to Step 2 registration
- Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
Exclusion Criteria:
STEP 2 REGISTRATION: Prior therapy for tumor except for resection. For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery
- Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent
- STEP 2 REGISTRATION: Current or planned treatment with any other investigational agents for the study cancer
- STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease outside the brain
- STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
- STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
- STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to the potential teratogenic effects and potential risk for adverse events in nursing infants
- STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or lomustine
- STEP 2 REGISTRATION: History of pulmonary fibrosis
STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatment
- Symptomatic congestive heart failure, defined as New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
- Unstable angina pectoris within 6 months prior to Step 2 registration
- Uncontrolled cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
Sites / Locations
- University of Arkansas for Medical SciencesRecruiting
- Kaiser Permanente-AnaheimRecruiting
- Kaiser Permanente-Deer Valley Medical CenterRecruiting
- Sutter Auburn Faith HospitalRecruiting
- Sutter Cancer Centers Radiation Oncology Services-AuburnRecruiting
- Alta Bates Summit Medical Center-Herrick CampusRecruiting
- Mercy Cancer Center �� CarmichaelRecruiting
- Mercy San Juan Medical CenterRecruiting
- John Muir Medical Center-Concord CampusRecruiting
- Kaiser Permanente DublinRecruiting
- Mercy Cancer Center - Elk GroveRecruiting
- Kaiser Permanente-FremontRecruiting
- Fresno Cancer CenterRecruiting
- Kaiser Permanente-FresnoRecruiting
- Kaiser Permanente Los Angeles Medical CenterRecruiting
- Kaiser Permanente-ModestoRecruiting
- Kaiser Permanente Oakland-BroadwayRecruiting
- Kaiser Permanente-OaklandRecruiting
- Kaiser Permanente-OntarioRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Kaiser Permanente-Rancho Cordova Cancer CenterRecruiting
- Kaiser Permanente- Marshall Medical OfficesRecruiting
- Kaiser Permanente-RichmondRecruiting
- Mercy Cancer Center - RocklinRecruiting
- Rohnert Park Cancer CenterRecruiting
- Kaiser Permanente-RosevilleRecruiting
- Sutter Cancer Centers Radiation Oncology Services-RosevilleRecruiting
- Sutter Roseville Medical CenterRecruiting
- The Permanente Medical Group-Roseville Radiation OncologyRecruiting
- Kaiser Permanente Downtown CommonsRecruiting
- Mercy Cancer Center - SacramentoRecruiting
- Sutter Medical Center SacramentoRecruiting
- Kaiser Permanente-South SacramentoRecruiting
- South Sacramento Cancer CenterRecruiting
- Kaiser Permanente-San Diego ZionRecruiting
- Kaiser Permanente-San FranciscoRecruiting
- Kaiser Permanente-Santa Teresa-San JoseRecruiting
- Kaiser Permanente San LeandroRecruiting
- Kaiser San Rafael-GallinasRecruiting
- Kaiser Permanente Medical Center - Santa ClaraRecruiting
- Kaiser Permanente-Santa RosaRecruiting
- Kaiser Permanente Cancer Treatment CenterRecruiting
- Kaiser Permanente-South San FranciscoRecruiting
- Kaiser Permanente-StocktonRecruiting
- Kaiser Permanente Medical Center-VacavilleRecruiting
- Kaiser Permanente-VallejoRecruiting
- Kaiser Permanente-Walnut CreekRecruiting
- John Muir Medical Center-Walnut CreekRecruiting
- Woodland Memorial HospitalRecruiting
- Rocky Mountain Cancer Centers-PenroseRecruiting
- UCHealth Memorial Hospital CentralRecruiting
- Memorial Hospital NorthRecruiting
- Poudre Valley HospitalRecruiting
- Cancer Care and Hematology-Fort CollinsRecruiting
- UCHealth Greeley HospitalRecruiting
- Littleton Adventist HospitalRecruiting
- Medical Center of the RockiesRecruiting
- Parker Adventist HospitalRecruiting
- Baptist MD Anderson Cancer CenterRecruiting
- Miami Cancer InstituteRecruiting
- Augusta University Medical CenterRecruiting
- Rush - Copley Medical CenterRecruiting
- Centralia Oncology ClinicRecruiting
- University of IllinoisRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Cancer Care Center of O'FallonRecruiting
- Advocate Lutheran General HospitalRecruiting
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- The Carle Foundation HospitalRecruiting
- Community Cancer Center SouthRecruiting
- Community Cancer Center NorthRecruiting
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- Mercy HospitalRecruiting
- Oncology Associates at Mercy Medical CenterRecruiting
- Medical Oncology and Hematology Associates-West Des MoinesRecruiting
- Mercy Cancer Center-West LakesRecruiting
- Greater Regional Medical CenterRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- Mission Cancer and Blood - LaurelRecruiting
- Mercy Medical Center-West LakesRecruiting
- University of Kansas Cancer CenterRecruiting
- University of Kansas Hospital-Indian Creek CampusRecruiting
- University of Kansas Hospital-Westwood Cancer CenterRecruiting
- Lafayette Family Cancer Center-EMMCRecruiting
- University of Maryland/Greenebaum Cancer CenterRecruiting
- Central Maryland Radiation Oncology in Howard CountyRecruiting
- UM Baltimore Washington Medical Center/Tate Cancer CenterRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Caro Cancer CenterRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Ascension Saint John HospitalRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Great Lakes Cancer Management Specialists-Van Elslander Cancer CenterRecruiting
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Borgess Medical CenterRecruiting
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Great Lakes Cancer Management Specialists-Macomb Medical CampusRecruiting
- Saint Mary's Oncology/Hematology Associates of MarletteRecruiting
- 21st Century Oncology-PontiacRecruiting
- Saint Joseph Mercy OaklandRecruiting
- Ascension Saint Mary's HospitalRecruiting
- Oncology Hematology Associates of Saginaw Valley PCRecruiting
- Ascension Saint Joseph HospitalRecruiting
- Saint John Macomb-Oakland HospitalRecruiting
- Saint Mary's Oncology/Hematology Associates of West BranchRecruiting
- University of Michigan Health - WestRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Sanford Joe Lueken Cancer CenterRecruiting
- Fairview Ridges Hospital
- Minnesota Oncology - BurnsvilleRecruiting
- Mercy HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Unity HospitalRecruiting
- Fairview Clinics and Surgery Center Maple GroveRecruiting
- Minnesota Oncology Hematology PA-MaplewoodRecruiting
- Saint John's Hospital - HealtheastRecruiting
- Abbott-Northwestern HospitalRecruiting
- Hennepin County Medical CenterRecruiting
- Health Partners Inc
- Monticello Cancer CenterRecruiting
- North Memorial Medical Health CenterRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Lakeview HospitalRecruiting
- Ridgeview Medical CenterRecruiting
- Saint Francis Medical CenterRecruiting
- Siteman Cancer Center at West County HospitalRecruiting
- Parkland Health Center - FarmingtonRecruiting
- Research Medical Center
- Washington University School of MedicineRecruiting
- Siteman Cancer Center-South CountyRecruiting
- Missouri Baptist Medical CenterRecruiting
- Siteman Cancer Center at Christian HospitalRecruiting
- Mercy Hospital Saint LouisRecruiting
- Siteman Cancer Center at Saint Peters HospitalRecruiting
- Sainte Genevieve County Memorial HospitalRecruiting
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Saint Barnabas Medical CenterRecruiting
- Jersey Shore Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey
- University of New Mexico Cancer Center
- Sands Cancer CenterRecruiting
- Noyes Memorial Hospital/Myers Cancer CenterRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- University of RochesterRecruiting
- Sanford Bismarck Medical CenterRecruiting
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- Cleveland Clinic Akron GeneralRecruiting
- Dayton Physicians LLC-Miami Valley SouthRecruiting
- Miami Valley Hospital SouthRecruiting
- Adena Regional Medical CenterRecruiting
- MetroHealth Medical CenterRecruiting
- Cleveland Clinic FoundationRecruiting
- Ohio State University Comprehensive Cancer CenterRecruiting
- Dayton Physician LLC-Miami Valley Hospital NorthRecruiting
- Miami Valley Hospital NorthRecruiting
- ProMedica Flower HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Mount Hood Medical CenterRecruiting
- Providence Newberg Medical CenterRecruiting
- Legacy Good Samaritan Hospital and Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Kaiser Permanente NorthwestRecruiting
- Legacy Meridian Park HospitalRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Geisinger Medical CenterRecruiting
- Geisinger Medical Oncology-LewisburgRecruiting
- Geisinger Cancer Services-PottsvilleRecruiting
- Reading HospitalRecruiting
- Geisinger Wyoming Valley/Henry Cancer CenterRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Avera Cancer InstituteRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Avera Cancer Institute at YanktonRecruiting
- Parkland Memorial HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Central Vermont Medical Center/National Life Cancer TreatmentRecruiting
- University of Vermont Medical CenterRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- Norris Cotton Cancer Center-NorthRecruiting
- Inova Alexandria HospitalRecruiting
- Inova Schar Cancer InstituteRecruiting
- Inova Fair Oaks HospitalRecruiting
- Bon Secours Memorial Regional Medical CenterRecruiting
- Bon Secours Saint Francis Medical CenterRecruiting
- Bon Secours Saint Mary's HospitalRecruiting
- Bon Secours Cancer Institute at Reynolds CrossingRecruiting
- VCU Massey Cancer Center at Stony PointRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Virginia Mason Medical CenterRecruiting
- Legacy Cancer Institute Medical Oncology and Day TreatmentRecruiting
- Legacy Salmon Creek HospitalRecruiting
- Langlade Hospital and Cancer CenterRecruiting
- Aurora Cancer Care-Southern Lakes VLCCRecruiting
- Aurora Health Care Germantown Health CenterRecruiting
- Aurora Cancer Care-GraftonRecruiting
- Aurora BayCare Medical CenterRecruiting
- UW Cancer Center Johnson CreekRecruiting
- Aurora Cancer Care-Kenosha SouthRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Aurora Bay Area Medical Group-MarinetteRecruiting
- Aurora Cancer Care-MilwaukeeRecruiting
- Aurora Saint Luke's Medical CenterRecruiting
- Aurora Sinai Medical CenterRecruiting
- ProHealth D N Greenwald CenterRecruiting
- Cancer Center of Western WisconsinRecruiting
- ProHealth Oconomowoc Memorial HospitalRecruiting
- Vince Lombardi Cancer Clinic - OshkoshRecruiting
- Aurora Cancer Care-RacineRecruiting
- Ascension Saint Mary's HospitalRecruiting
- Vince Lombardi Cancer Clinic-SheboyganRecruiting
- Ascension Saint Michael's HospitalRecruiting
- Aurora Medical Center in SummitRecruiting
- Vince Lombardi Cancer Clinic-Two RiversRecruiting
- UW Cancer Center at ProHealth CareRecruiting
- Aspirus Regional Cancer CenterRecruiting
- Aurora Cancer Care-Milwaukee WestRecruiting
- Aurora West Allis Medical CenterRecruiting
- Aspirus Cancer Care - Wisconsin RapidsRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (radiation therapy, temozolomide)
ARM II (radiation therapy, temozolomide, lomustine)
Patients undergo radiation therapy 5 days per week and receive temozolomide PO QD for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive lomustine PO on day 1 and temozolomide PO QD on days 2-6. Treatment repeats every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity.