Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma
A Safety Run-In and Phase II Study Evaluating the Efficacy, Safety, and Impact on the Tumor Microenvironment of the Combination of Tocilizumab, Atezolizumab, and Fractionated Stereotactic Radiotherapy in Recurrent Glioblastoma
3 other identifiers
interventional
59
1 country
110
Brief Summary
This phase II trial studies the best dose and effect of tocilizumab in combination with atezolizumab and stereotactic radiation therapy in treating glioblastoma patients whose tumor has come back after initial treatment (recurrent). Tocilizumab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6), which is made by white blood cells and other cells in the body as well as certain types of cancer. This may help lower the body's immune response and reduce inflammation. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Fractionated stereotactic radiation therapy uses special equipment to precisely deliver multiple, smaller doses of radiation spread over several treatment sessions to the tumor. The goal of this study is to change a tumor that is unresponsive to cancer therapy into a more responsive one. Therapy with fractionated stereotactic radiotherapy in combination with tocilizumab may suppress the inhibitory effect of immune cells surrounding the tumor and consequently allow an immunotherapy treatment by atezolizumab to activate the immune response against the tumor. Combination therapy with tocilizumab, atezolizumab and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation therapy alone in patients with recurrent glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2022
Typical duration for phase_2
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2021
CompletedFirst Posted
Study publicly available on registry
January 29, 2021
CompletedStudy Start
First participant enrolled
March 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 15, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 4, 2026
ExpectedApril 1, 2026
March 1, 2026
3.3 years
January 28, 2021
March 31, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Dose-limiting toxicities (Safety Run-In)
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0.
Up to 1 post-fractionated stereotactic radiation therapy (FRST) cycle of systemic therapy for which dose-limiting toxicity is reached (1 cycle = 4 weeks)
Maximum-tolerated dose (Safety Run-In)
Up to 1 post-FRST cycle of systemic therapy for which dose-limiting toxicity is reached (1 cycle = 4 weeks)
Objective radiographic response rate (Phase II, Non-Surgical Cohort)
Will be determined using modified Response Assessment in Neuro-oncology with the pretreatment magnetic resonance imaging as baseline. Frequencies and percent of responses will be provided for patients with measurable disease.
Up to 6 months from enrollment
Secondary Outcomes (5)
Progression-free survival (PFS) (Phase II, Non-Surgical Cohort)
Time from study enrollment to disease progression or death from any cause, assessed up to 2 years
Overall survival (Phase II, Non-Surgical Cohort)
From study enrollment to death from any cause, assessed up to 2 years
Progression-free survival (Phase II, Non-Surgical Cohort)
From randomization to disease progression or death from any cause, assessed up to 2 years
Overall survival (Phase II, Surgical Cohort)
From study enrollment to death from any cause, assessed up to 2 years
Incidence of adverse events (Surgical Cohort and Non-Surgical Cohort)
Up to 2 years
Other Outcomes (1)
Immune response (Phase II, Surgical Cohort)
Baseline and cycle 2, day 1 (1 cycle = 4 weeks)
Study Arms (3)
Group I (tocilizumab, atezolizumab, FSRT)
EXPERIMENTALPatients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days in the absence of disease progression or unacceptable toxicity. Starting 4 weeks from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial.
Group II, Arm I (tocilizumab, atezolizumab, FSRT, surgery)
EXPERIMENTALPatients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial, as well as blood sample and tumor tissue collection on study.
Group II, Arm II (tocilizumab, atezolizumab, FSRT, surgery)
EXPERIMENTALPatients receive systemic treatment with atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3-5 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-42 days from the first dose of systemic treatment, patients resume treatment with tocilizumab IV over 60 minutes with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and tumor tissue collection on study. Patients undergo MRI throughout the trial, as well as blood sample and tumor tissue collection on study.
Interventions
Given IV
Undergo blood sample and tumor tissue collection
Undergo surgery
Undergo FSRT
Undergo MRI
Given IV
Eligibility Criteria
You may qualify if:
- Histopathologically proven diagnosis of glioblastoma, OR molecular diagnosis of glioblastoma per Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (c-IMPACT-NOW) criteria ("diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, World Health Organization \[WHO\] grade IV"; this requires presence of amplification of EGFR, whole chromosome 7 gain AND whole chromosome 10 loss, or TERT promoter mutation)
- Tumor that is in first recurrence following prior first-line radiation therapy (prior dose \>= 40 Gy)
- Note: Prior temozolomide, prior tumor-treating fields, and/or Gliadel wafers (if placed at initial tumor resection) are allowed, but none of these are required
- Unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan within 21 days prior to registration
- Per radiation oncologist review of MRI within 21 days prior to registration, must have focus of progressive, contrast-enhancing tumor that is amenable to FSRT, defined as the following:
- At least 1 cm x 1 cm contrast-enhancing tumor that is no greater than 4 cm in largest dimension
- FSRT target is at least 0.5 cm from the optic chiasm and brainstem
- Note, multifocal disease (i.e., other sites of tumor beyond the tumor being targeted for FSRT) is allowed if the above criteria are met for the tumor that is the proposed target for FSRT
- Surgical cohort only (Phase II only):
- Must be a candidate for repeat surgery (significant debulking or gross total resection of the contrast enhancing area) as determined by the neurosurgeon or multidisciplinary team
- Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available from any prior GBM tumor specimen; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction \[MSPCR\] or quantitative polymerase chain reaction \[PCR\]) are acceptable)
- The following intervals from previous treatments to registration are required to be eligible:
- If prior radiation was \< 60 Gy, an interval of at least 12 weeks (84 days) must have elapsed since the completion of radiation therapy
- If prior radiation was \>= 60 Gy, an interval of least 6 months (182 days) must have elapsed since the completion of radiation therapy, unless the target lesion for FSRT is outside of the 80% isodose line of the original radiation plan
- At least 21 days from temozolomide
- +26 more criteria
You may not qualify if:
- Known somatic tumor mutation in IDH1 or IDH2 gene. If not previously completed, sequencing of the IDH1 and IDH2 genes is not required to determine trial eligibility
- Known germline DNA repair defect (mismatch repair deficiency, POLE mutation, e.g.). If not previously completed, germline sequencing is not required to determine trial eligibility
- Diffuse leptomeningeal disease
- Known contrast-enhancing tumor in brainstem or spinal cord. If not previously completed, spinal imaging is not required to determine trial eligibility
- Patients with clinically significant mass effect or midline shift (e.g., 1-2 cm of midline shift)
- Prior bevacizumab therapy
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded from this trial. Otherwise, patients with prior or concurrent malignancy are eligible
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or pathway-targeting agents
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 4 weeks prior to registration
- Treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to registration
- Systemic corticosteroids used to treat brain edema and/or related symptoms at a dose of \> 2 mg of dexamethasone (or equivalent) daily within 5 days prior to registration. Patients receiving systemic corticosteroids for other indications are excluded
- Patients with increased risk for gastrointestinal perforations including history of diverticulitis
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologycollaborator
- National Cancer Institute (NCI)lead
Study Sites (110)
Kaiser Permanente-Anaheim
Anaheim, California, 92806, United States
Kaiser Permanente-Bellflower
Bellflower, California, 90706, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Kaiser Permanente-Ontario
Ontario, California, 91761, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661, United States
Sutter Roseville Medical Center
Roseville, California, 95661, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Kaiser Permanente-San Diego Zion
San Diego, California, 92120, United States
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909, United States
Memorial Hospital North
Colorado Springs, Colorado, 80920, United States
Poudre Valley Hospital
Fort Collins, Colorado, 80524, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528, United States
UCHealth Greeley Hospital
Greeley, Colorado, 80631, United States
Medical Center of the Rockies
Loveland, Colorado, 80538, United States
Boca Raton Regional Hospital
Boca Raton, Florida, 33486, United States
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704, United States
Illinois CancerCare-Canton
Canton, Illinois, 61520, United States
Illinois CancerCare-Carthage
Carthage, Illinois, 62321, United States
Centralia Oncology Clinic
Centralia, Illinois, 62801, United States
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Illinois CancerCare-Eureka
Eureka, Illinois, 61530, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401, United States
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443, United States
Illinois CancerCare-Macomb
Macomb, Illinois, 61455, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350, United States
Illinois CancerCare-Pekin
Pekin, Illinois, 61554, United States
Illinois CancerCare-Peoria
Peoria, Illinois, 61615, United States
OSF Saint Francis Medical Center
Peoria, Illinois, 61637, United States
Illinois CancerCare-Peru
Peru, Illinois, 61354, United States
Illinois CancerCare-Princeton
Princeton, Illinois, 61356, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Illinois CancerCare - Washington
Washington, Illinois, 61571, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214, United States
MaineHealth Maine Medical Center - Portland
Portland, Maine, 04102, United States
MaineHealth Cancer Care Center of York County
Sanford, Maine, 04073, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074, United States
MaineHealth Cancer Care and IV Therapy - South Portland
South Portland, Maine, 04106, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655, United States
Research Medical Center
Kansas City, Missouri, 64132, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Renown Regional Medical Center
Reno, Nevada, 89502, United States
Jersey Shore Medical Center
Neptune City, New Jersey, 07753, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030, United States
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210, United States
Legacy Meridian Park Hospital
Tualatin, Oregon, 97062, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
UPMC-Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
Geisinger Cancer Services-Pottsville
Pottsville, Pennsylvania, 17901, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Bon Secours Saint Francis Medical Center
Midlothian, Virginia, 23114, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Valley Medical Center
Renton, Washington, 98055, United States
Legacy Cancer Institute Medical Oncology and Day Treatment
Vancouver, Washington, 98684, United States
Legacy Salmon Creek Hospital
Vancouver, Washington, 98686, United States
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409, United States
Aspirus Cancer Care - James Beck Cancer Center
Rhinelander, Wisconsin, 54501, United States
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin, 54481, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188, United States
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401, United States
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen J Bagley
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2021
First Posted
January 29, 2021
Study Start
March 11, 2022
Primary Completion
June 15, 2025
Study Completion (Estimated)
September 4, 2026
Last Updated
April 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.