AzTrials
AzTrials

Diffuse Astrocytoma, IDH-WildtypePhase 2NCT04729959

Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma

A Phase 2 study testing Atezolizumab, Biospecimen Collection and Conventional Surgery in people with Diffuse Astrocytoma, IDH-Wildtype and Recurrent Glioblastoma, run by National Cancer Institute (NCI) at 110 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Biospecimen Collection and Conventional Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
110 sitesUnited States
Study dates
11 Mar 2022to 20 Aug 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • At least 28 days from any investigational (not Food and Drug Administration [FDA]-approved for glioblastoma) agents, or within a time interval less than at least 5 half-lives of the investigational agent whichever is shorter (Note: anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or pathway-targeting agents are not allowed)
  • Age >= 18 years
  • Karnofsky performance status >= 70 within 14 days prior to registration
  • History/physical examination within 14 days prior to registration
  • Leukocytes >= 2,500/mm^3 (within 14 days prior to registration)
  • Absolute neutrophil count >= 1,500/mm^3 (within 14 days prior to registration)
  • Absolute lymphocyte count >= 800/mm^3 (within 14 days prior to registration)
  • Platelets >= 100,000/mm^3 (within 14 days prior to registration)
  • Hemoglobin >= 8 g/dL (within 14 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x ULN (within 14 days prior to registration)
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN (within 14 days prior to registration)
  • Alkaline phosphatase =< 2.5 x ULN (within 14 days prior to registration)
  • Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault (within 14 days prior to registration)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of receipt of study treatment, and for 60 days (males) or 90 days (females) from the last dose of tocilizumab and for 5 months (150 days) after the last dose of atezolizumab. Administration of atezolizumab or tocilizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration
  • Patients positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive patients must have:
  • An undetectable viral load within 6 months of registration
  • A stable regimen of highly active anti-retroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • 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
  • 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
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Availability of prior radiotherapy treatment plan details in Digital Imaging and Communications in Medicine (DICOM) format

Who cannot join

  • 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
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  • 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
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
  • Note: patients with the below conditions are eligible:
  • Autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
  • Controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
  • Eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.)
  • Note: History of radiation pneumonitis in a prior radiation field (fibrosis) is permitted
  • Patients with active tuberculosis (TB) are excluded
  • Severe infections within 3 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 1 week prior to registration
  • Received oral or intravenous (IV) antibiotics within 2 weeks prior to registration
  • Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Major surgical procedure within 21 days prior to registration or anticipation of need for a major surgical procedure during the course of study treatment
  • Administration of a live, attenuated vaccine within 4 weeks before registration or anticipation that such a live, attenuated vaccine will be required during receipt of study treatment and up to 5 months after the last dose of study drug
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women who are pregnant or nursing (and unwilling to discontinue) are excluded from this study. Atezolizumab and tocilizumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab and tocilizumab breastfeeding should be discontinued if the mother is treated with atezolizumab and tocilizumab

Trial locations and contacts

110 sites in 1 country.

110 sites in 1 country

United States110 sites

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, 80528

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • UCHealth Greeley Hospital

    Greeley, Colorado, 80631

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Research Medical Center

    Kansas City, Missouri, 64132

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Medical Center of the Rockies

    Loveland, Colorado, 80538

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Miami Cancer Institute

    Miami, Florida, 33176

  • Bon Secours Saint Francis Medical Center

    Midlothian, Virginia, 23114

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Jersey Shore Medical Center

    Neptune City, New Jersey, 07753

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Kaiser Permanente-Ontario

    Ontario, California, 91761

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • UPMC-Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • MaineHealth Maine Medical Center - Portland

    Portland, Maine, 04102

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Geisinger Cancer Services-Pottsville

    Pottsville, Pennsylvania, 17901

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Valley Medical Center

    Renton, Washington, 98055

  • Aspirus Cancer Care-Rhinelander-James Beck Cancer Center

    Rhinelander, Wisconsin, 54501

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • Sutter Roseville Medical Center

    Roseville, California, 95661

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Kaiser Permanente-San Diego Zion

    San Diego, California, 92120

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • MaineHealth Cancer Care Center of York County

    Sanford, Maine, 04073

  • MaineHealth Maine Medical Center- Scarborough

    Scarborough, Maine, 04074

  • Sanford Cancer Center Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • MaineHealth Cancer Care and IV Therapy - South Portland

    South Portland, Maine, 04106

  • Aspirus Cancer Care - Stevens Point

    Stevens Point, Wisconsin, 54481

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Legacy Meridian Park Hospital

    Tualatin, Oregon, 97062

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Legacy Cancer Institute Medical Oncology and Day Treatment

    Vancouver, Washington, 98684

  • Legacy Salmon Creek Hospital

    Vancouver, Washington, 98686

  • Illinois CancerCare - Washington

    Washington, Illinois, 61571

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aspirus Cancer Care-Wausau

    Wausau, Wisconsin, 54401

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Ascension Via Christi Hospitals Wichita

    Wichita, Kansas, 67214

  • Geisinger Wyoming Valley/Henry Cancer Center

    Wilkes-Barre, Pennsylvania, 18711

  • Aspirus Cancer Care - Wisconsin Rapids

    Wisconsin Rapids, Wisconsin, 54494

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated dose (MTD) among three sequential dose levels: single-agent tocilizumab 4 mg/kg, single-agent tocilizumab 8 mg/kg, and tocilizumab 8 mg/kg + atezolizumab 1680 mg (each administered with fractionated stereotactic radiation therapy [FSRT]), to be used for subsequent phase II testing. (Safety Run-In) II. To determine the efficacy of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT in recurrent glioblastoma (GBM), as measured by the objective radiographic response rate (ORR). (Phase II [Non-Surgical Cohort])

SECONDARY OBJECTIVES:

  1. To estimate the progression-free survival (PFS) in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R) and FSRT (and atezolizumab [anti-PD-L1], if dose level 3 is MTD). (Phase II Non-Surgical Cohort and Safety Run-in Cohort) II. To estimate the overall survival (OS) in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R) and FSRT (and atezolizumab [anti-PD-L1], if dose level 3 is MTD)), atezolizumab (anti-PD-L1), and FSRT. (Phase II Non-Surgical Cohort and Safety Run-in Cohort) III. To estimate the progression-free survival (PFS) in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT. (Phase II Surgical Cohort) IV. To estimate the overall survival (OS) in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT. (Phase II Surgical Cohort) V. To determine the rate and severity of adverse events (AEs) of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT in recurrent glioblastoma according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. (Separately in the Nonsurgical and Surgical Cohorts)

EXPLORATORY OBJECTIVES:

  1. To determine the effect of the combination of atezolizumab (anti-PD-L1) and FSRT, with versus (vs.) without tocilizumab (anti-IL6R), on the GBM immune microenvironment. (Phase II Surgical Cohort) II. To evaluate the pharmacodynamic impact of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT on peripheral blood immune cell populations. (Phase II Surgical Cohort) III. To detect tumor and/or blood biomarkers associated with the outcomes of OS, PFS, and/or ORR in patients with recurrent GBM treated with the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT. (Phase II Non-Surgical Cohort)

OUTLINE:

SAFETY RUN-IN, ARM 1 (Non Surgical Cohort: Dose Level 1): The non-surgical cohort is defined as patients with recurrent glioblastoma without a clinical indication for surgical resection. Patients receive tocilizumab 4 mg/kg administered intravenously (IV) over 60 minutes on Day 1. Within 3-7 days, patients undergo fractionated stereotactic radiotherapy (FSRT) delivered in 3 fractions over 3-5 days in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the first dose, patients resume tocilizumab every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) throughout the study. (CLOSED TO ACCRUAL 08-AUG-2023)

SAFETY RUN-IN, ARM 2 (Non Surgical Cohort: Dose Level 2): Patients receive tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL 08-AUG-2023)

SAFETY RUN-IN, ARM 3 (Non Surgical Cohort: Dose Level 3): Patients receive atezolizumab administered intravenously (IV) over 30-60 minutes followed by tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume atezolizumab plus tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL 08-AUG-2023)

NON SURGICAL COHORT, ARM 4 (Phase II Expansion): The non-surgical cohort is defined as patients with recurrent glioblastoma without a clinical indication for surgical resection. Patients receive atezolizumab IV followed by tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume atezolizumab plus tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity.

SURGICAL COHORT, ARM A: The surgical cohort is defined as patients with recurrent glioblastoma with a clinical indication for surgical resection. Patients receive atezolizumab IV followed by tocilizumab 8 mg/kg IV on Day 1. Within 3-7 days, patients undergo FSRT delivered in 3 fractions over 3-5 days, followed by surgical resection 7-14 days after completion of FSRT. Beginning 21-42 days after surgery, patients receive atezolizumab plus tocilizumab every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study, and blood and tumor tissue are collected on study.

SURGICAL COHORT, ARM B: Patients receive atezolizumab IV alone on Day 1 prior to FSRT and surgery. FSRT timing and fractionation, surgical timing, post operative treatment, MRI assessments, and biospecimen collection are performed as described in Arm A.

After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, 12, 18, and 24 months.

Being tested
Atezolizumab, Biospecimen Collection, Conventional Surgery, Fractionated Stereotactic Radiation Therapy, Magnetic Resonance Imaging
Medical subject headings
Astrocytoma, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabBiological

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample and tumor tissue collection

  • Conventional SurgeryProcedure or surgery

    Undergo surgery

  • Fractionated Stereotactic Radiation TherapyRadiation

    Also called Fractionated Stereotactic Radiotherapy

    Undergo FSRT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • TocilizumabBiological

    Also called Actemra, Avtozma, IL-6 receptor monoclonal antibodies: tocilizumab, Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer

    Given IV

Study groups in NCT04729959
Study groupRoleWhat they receive
Non Surgical Cohort: Arm 1 - Level 1 (tocilizumab)ExperimentalThe non-surgical cohort is defined as patients with recurrent glioblastoma without a clinical indication for surgical resection. Patients receive tocilizumab 4 mg/kg administered intravenously (IV) over 60 minutes on Day 1. Within 3-7 days, patients undergo FSRT delivered in 3 fractions over 3-5 days in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the first dose, patients resume tocilizumab every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Tocilizumab
Non Surgical Cohort: Arm 2 - Level 2 (tocilizumab)ExperimentalPatients receive tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Tocilizumab
Non Surgical Cohort: Arm 4 (tocilizumab, atezolizumab)ExperimentalThe non-surgical cohort is defined as patients with recurrent glioblastoma without a clinical indication for surgical resection. Patients receive atezolizumab IV followed by tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume atezolizumab plus tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Tocilizumab
Non Surgical Cohort:Arm 3- Level 3 (tocilizumab, atezolizumab)ExperimentalPatients receive atezolizumab administered IV over 30-60 minutes followed by tocilizumab 8 mg/kg IV on Day 1. FSRT timing and fractionation, treatment schedule, and MRI assessments are performed as described in Arm 1. Beginning 4 weeks after the first dose, patients resume atezolizumab plus tocilizumab every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Tocilizumab
Surgical Cohort: Arm A - Neoadjuvant Tocilizumab+AtezolizumabExperimentalThe surgical cohort is defined as patients with recurrent glioblastoma with a clinical indication for surgical resection. Patients receive atezolizumab IV followed by tocilizumab 8 mg/kg IV on Day 1. Within 3-7 days, patients undergo FSRT delivered in 3 fractions over 3-5 days, followed by surgical resection 7-14 days after completion of FSRT. Beginning 21-42 days after surgery, patients receive atezolizumab plus tocilizumab every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study, and blood and tumor tissue are collected on study.
Receives: Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Tocilizumab
Surgical Cohort: Arm B - Neoadjuvant Atezolizumab AloneExperimentalPatients receive atezolizumab IV alone on Day 1 prior to FSRT and surgery. FSRT timing and fractionation, surgical timing, post operative treatment, MRI assessments, and biospecimen collection are performed as described in Arm A.
Receives: Biological: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Conventional Surgery; Radiation: Fractionated Stereotactic Radiation Therapy; Procedure: Magnetic Resonance Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. [Non-surgical Cohort] Maximum-tolerated Dose (Safety Run-In)

    The maximum tolerated dose (MTD) was defined as the highest prespecified dose level with an observed dose-limiting toxicity (DLT) rate of ≤33% of participants. MTD was determined during the safety run-in by testing increasing prespecified dose levels of tocilizumab alone and in combination with atezolizumab in Arms 1-3, with cohorts of 3 to 6 participants enrolled at each dose level. Dose escalation began with tocilizumab 4 mg/kg (Dose Level 1 / Arm 1), followed by tocilizumab 8 mg/kg (Dose Level 2 / Arm 2), and then tocilizumab 8 mg/kg in combination with atezolizumab 1680 mg (Dose Level 3 / Arm 3).

    Measured: From first dose of study drug through completion of Cycle 1 (28 days).

  2. [Non-surgical Cohort, Safety Run-In] Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    DLTs per NCI CTCAE v5.0 include Grade ≥2 toxicity at least possibly related to study drug(s) that does not resolve to Grade ≤1 within 6 weeks of last dose with optimal management or prevents tapering corticosteroids to baseline (or pre-toxicity dose) within 6 weeks, excluding CNS toxicity due to intratumoral/peritumoral disease or edema that improves to Grade ≤2 within 7 days, cerebral edema improving per protocol, or endocrinopathy controlled by hormone replacement. Additional DLTs include Grade 4 immune-related AEs (excluding controlled endocrinopathy); Grade 3 hepatitis, pneumonitis, nephritis, myocarditis, pericarditis, encephalitis, myasthenia gravis, uveitis, episcleritis, peripheral neuropathy, autoimmune hemolytic anemia, acquired hemophilia, or autonomic neuropathy; recurrent Grade 2 pneumonitis; any-grade transverse myelitis; and hepatic or hematologic toxicity meeting protocol-specified criteria for dose modification or discontinuation.

    Measured: From first dose of study drug through completion of Cycle 1 (28 days).

  3. [Non-surgical Cohort] Objective Radiographic Response Rate (Phase II)

    Objective radiographic response rate (ORR) is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) on magnetic resonance imaging (MRI) using modified Response Assessment in Neuro-Oncology (RANO) criteria, compared with baseline MRI. CR is disappearance of all enhancing disease with no new lesions. PR is ≥50% decrease in enhancing tumor burden. Responses must be sustained for ≥4 weeks.

    Measured: Registration to 6 months

Secondary outcomes (5)

  1. [Phase II Non-Surgical Cohort] Progression-free Survival

    Disease progression is assessed by modified RANO criteria with iRANO adaptations. Progressive disease is defined as ≥25% increase in enhancing tumor burden compared with nadir, appearance of new enhancing lesions, clear clinical deterioration attributable to tumor progression, progression of non-measurable disease, or death. For patients receiving immunotherapy, suspected progression within 6 months may require confirmation on subsequent imaging to account for pseudoprogression; confirmed progression is back-dated to the initial scan. Median progression-free survival time was estimated using the Kaplan-Meier method, censoring participants alive without progression at date of the last evaluable MRI tumor assessment.

    Measured: Time from study enrollment to disease progression, death from any cause, or last evaluable MRI tumor assessment. Maximum follow-up time at time of analysis was 13.5 months.

  2. [Phase II Non-Surgical Cohort] Overall Survival

    Median survival time was estimated using the Kaplan-Meier method in which participants alive at last known follow-up are censored.

    Measured: From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.5 months.

  3. [Surgical Cohort] Progression-free Survival

    Disease progression is assessed by modified RANO criteria with iRANO adaptations. Progressive disease is defined as ≥25% increase in enhancing tumor burden compared with nadir, appearance of new enhancing lesions, clear clinical deterioration attributable to tumor progression, progression of non-measurable disease, or death. For patients receiving immunotherapy, suspected progression within 6 months may require confirmation on subsequent imaging to account for pseudoprogression; confirmed progression is back-dated to the initial scan. Median progression-free survival time was estimated using the Kaplan-Meier method, censoring participants alive without progression at date of the last evaluable MRI tumor assessment.

    Measured: Time from study enrollment to disease progression, death from any cause, or last evaluable MRI tumor assessment. Maximum follow-up time at time of analysis was 13.9 months.

  4. [Surgical Cohort] Overall Survival

    Median survival time was estimated using the Kaplan-Meier method in which participants alive at last known follow-up are censored.

    Measured: From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.9 months.

  5. Number of Participants by Highest Grade Adverse Event Reported

    National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Measured: From study enrollment to last follow-up. Maximum follow-up time at time of analysis was 13.5 months for non-surgical cohort Arm 4, 13.9 months for surgical cohort Arms A and B, and 23.5 months for the non-surgical safety run-in Arms 1-3.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2021
  2. Study start11 Mar 2022
  3. Primary completion15 Jun 2025
  4. Study completion20 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04729959
Sponsor's protocol ID
NCI-2021-00410
Other IDs
NCI-2021-00410, NRG-BN010, NRG-BN010, U10CA180868
Status last verified
Sep 2026
First submitted
28 Jan 2021
Last updated
23 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Biospecimen Collection and Conventional Surgery in people with Diffuse Astrocytoma, IDH-Wildtype and Recurrent Glioblastoma, run by National Cancer Institute (NCI) at 110 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

[Non-surgical Cohort] Maximum-tolerated Dose (Safety Run-In) (time frame: From first dose of study drug through completion of Cycle 1 (28 days).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04729959.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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