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ACTIVE NOT RECRUITING

NCT05095376

PHASE3

Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma

Sponsor: NRG Oncology

View on ClinicalTrials.gov

Summary

This phase III trial compares the effect of adding lomustine to standard chemotherapy with temozolomide and radiation therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly diagnosed MGMT methylated glioblastoma. MGMT methylated tumors are more likely to respond to temozolomide chemotherapy. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's DNA and may kill tumor cells. Radiation therapy uses high energy x-ray photons to kill tumor cells and shrink tumors. Adding lomustine to standard chemotherapy with temozolomide and radiation therapy may shrink or stabilize glioblastoma.

Official title: A Phase III Trial of Lomustine-Temozolomide Combination Therapy Versus Standard Temozolomide in Patients With Methylated MGMT Promoter Glioblastoma

Key Details

Gender

All

Age Range

18 Years - 70 Years

Study Type

INTERVENTIONAL

Enrollment

265

Start Date

2022-03-28

Completion Date

2026-08-08

Last Updated

2026-04-03

Healthy Volunteers

Conditions

Glioblastoma Gliosarcoma

Interventions

DRUG

Lomustine

Given PO

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

RADIATION

Photon Beam Radiation Therapy

Undergo radiation therapy

OTHER

Questionnaire Administration

Ancillary studies

DRUG

Temozolomide

Given PO

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 New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 30. If tissue cannot be received by postoperative calendar day 30, 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 8 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be completed within 10 business days of receipt of tissue. Results will be entered by the central lab directly into Rave. Note: In the event of an additional tumor resection(s), tissue must be received within 30 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: 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. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded * Note: Any MGMT result other than methylated would require step 2 registration to be reported as a "central review failure" * STEP 2 REGISTRATION: Contrast-enhanced brain MRI performed either after surgery or prior to step 2 registration * 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) (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Leukocytes \>= 2,000/mm\^3 (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Absolute neutrophil count \>= 1,500/mm\^3 (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Platelets \>= 100,000/mm\^3 (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Total bilirubin =\< 1.5 x institutional/lab upper limit of normal (ULN) (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration) * STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (Within 14 days prior to step 2 registration) * 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 14 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 or prior laser interstitial thermal therapy (LITT). 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 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. Prior laser interstitial thermal therapy (LITT) is allowed * 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 intravenous (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 * STEP 2 REGISTRATION: Evidence of diffuse leptomeningeal disease that requires whole brain irradiation

Locations (420)

Fairbanks Memorial Hospital

Fairbanks, Alaska, United States

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Highlands Oncology Group - Rogers

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

Kaiser Permanente-Anaheim

Anaheim, California, United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

Sutter Auburn Faith Hospital

Auburn, California, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

Mercy Cancer Center - Carmichael

Carmichael, California, United States

Mercy San Juan Medical Center

Carmichael, California, United States

John Muir Medical Center-Concord

Concord, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Kaiser Permanente Dublin

Dublin, California, United States

Mercy Cancer Center - Elk Grove

Elk Grove, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Palo Alto Medical Foundation-Fremont

Fremont, California, United States

Fresno Cancer Center

Fresno, California, United States

Kaiser Permanente Fresno Orchard Plaza

Fresno, California, United States

Kaiser Permanente-Fresno

Fresno, California, United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Kaiser Permanente- Modesto MOB II

Modesto, California, United States

Kaiser Permanente-Modesto

Modesto, California, United States

Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Kaiser Permanente Oakland-Broadway

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Kaiser Permanente-Ontario

Ontario, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Palo Alto Medical Foundation Health Care

Palo Alto, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States

Kaiser Permanente- Marshall Medical Offices

Redwood City, California, United States

Kaiser Permanente-Richmond

Richmond, California, United States

Mercy Cancer Center - Rocklin

Rocklin, California, United States

Rohnert Park Cancer Center

Rohnert Park, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

Sutter Roseville Medical Center

Roseville, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States

Kaiser Permanente Downtown Commons

Sacramento, California, United States

Mercy Cancer Center - Sacramento

Sacramento, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

South Sacramento Cancer Center

Sacramento, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Kaiser San Rafael-Gallinas

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Sutter Pacific Medical Foundation

Santa Rosa, California, United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Kaiser Permanente-Stockton

Stockton, California, United States

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Woodland Memorial Hospital

Woodland, California, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado, United States

Lutheran Hospital - Cancer Centers of Colorado

Golden, Colorado, United States

UCHealth Greeley Hospital

Greeley, Colorado, United States

AdventHealth Littleton

Littleton, Colorado, United States

Medical Center of the Rockies

Loveland, Colorado, United States

AdventHealth Parker

Parker, Colorado, United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Augusta University Medical Center

Augusta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, United States

Alton Memorial Hospital

Alton, Illinois, United States

Rush-Copley Medical Center

Aurora, Illinois, United States

Advocate Outpatient Center - Aurora

Aurora, Illinois, United States

Advocate Good Shepherd Hospital

Barrington, Illinois, United States

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Illinois CancerCare-Canton

Canton, Illinois, United States

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Centralia Oncology Clinic

Centralia, Illinois, United States

Rush MD Anderson Cancer Center

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States

AMG Crystal Lake - Oncology

Crystal Lake, Illinois, United States

Carle at The Riverfront

Danville, Illinois, United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Advocate Good Samaritan Hospital

Downers Grove, Illinois, United States

Carle Physician Group-Effingham

Effingham, Illinois, United States

Crossroads Cancer Center

Effingham, Illinois, United States

Advocate Sherman Hospital

Elgin, Illinois, United States

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Advocate South Suburban Hospital

Hazel Crest, Illinois, United States

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

AMG Libertyville - Oncology

Libertyville, Illinois, United States

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Illinois CancerCare-Peru

Peru, Illinois, United States

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Memorial Hospital East

Shiloh, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Springfield Clinic

Springfield, Illinois, United States

Springfield Memorial Hospital

Springfield, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

The Carle Foundation Hospital

Urbana, Illinois, United States

Illinois CancerCare - Washington

Washington, Illinois, United States

Midwestern Regional Medical Center

Zion, Illinois, United States

Northwest Cancer Center - Main Campus

Crown Point, Indiana, United States

UChicago Medicine Northwest Indiana

Crown Point, Indiana, United States

Northwest Oncology LLC

Dyer, Indiana, United States

Northwest Cancer Center - Hobart

Hobart, Indiana, United States

Saint Mary Medical Center

Hobart, Indiana, United States

Community Cancer Center East

Indianapolis, Indiana, United States

Community Cancer Center South

Indianapolis, Indiana, United States

Community Cancer Center North

Indianapolis, Indiana, United States

The Community Hospital

Munster, Indiana, United States

Women's Diagnostic Center - Munster

Munster, Indiana, United States

Northwest Cancer Center - Valparaiso

Valparaiso, Indiana, United States

Mary Greeley Medical Center

Ames, Iowa, United States

McFarland Clinic - Ames

Ames, Iowa, United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

Mercy Hospital

Cedar Rapids, Iowa, United States

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Greater Regional Medical Center

Creston, Iowa, United States

Iowa Methodist Medical Center