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测试将免疫治疗药物 Tocilizumab 和 Atezolizumab 添加到复发性胶质母细胞瘤的放射治疗中

2026年9月22日 更新者：National Cancer Institute (NCI)

评估托珠单抗、阿特珠单抗和分次立体定向放疗联合治疗复发性胶质母细胞瘤的疗效、安全性和对肿瘤微环境影响的安全性磨合期和 II 期研究

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.

研究概览

地位

主动，不招人

条件

干预/治疗

详细说明

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

研究类型

介入性

注册 (实际的)

61

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • California
      • Anaheim、California、美国、92806
        • Kaiser Permanente-Anaheim
      • Bellflower、California、美国、90706
        • Kaiser Permanente-Bellflower
      • Los Angeles、California、美国、90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles、California、美国、90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles、California、美国、90033
        • Los Angeles General Medical Center
      • Ontario、California、美国、91761
        • Kaiser Permanente-Ontario
      • Orange、California、美国、92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Roseville、California、美国、95661
        • Sutter Cancer Centers Radiation Oncology Services-Roseville
      • Roseville、California、美国、95661
        • Sutter Roseville Medical Center
      • Sacramento、California、美国、95816
        • Sutter Medical Center Sacramento
      • Sacramento、California、美国、95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego、California、美国、92120
        • Kaiser Permanente-San Diego Zion
      • San Francisco、California、美国、94115
        • California Pacific Medical Center-Pacific Campus
    • Colorado
      • Aurora、Colorado、美国、80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs、Colorado、美国、80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs、Colorado、美国、80920
        • Memorial Hospital North
      • Fort Collins、Colorado、美国、80524
        • Poudre Valley Hospital
      • Fort Collins、Colorado、美国、80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley、Colorado、美国、80631
        • UCHealth Greeley Hospital
      • Loveland、Colorado、美国、80538
        • Medical Center of the Rockies
    • Florida
      • Boca Raton、Florida、美国、33486
        • Boca Raton Regional Hospital
      • Jacksonville、Florida、美国、32207
        • Baptist MD Anderson Cancer Center
      • Miami、Florida、美国、33176
        • Miami Cancer Institute
      • Orlando、Florida、美国、32806
        • Orlando Health Cancer Institute
      • Tampa、Florida、美国、33612
        • Moffitt Cancer Center
    • Illinois
      • Bloomington、Illinois、美国、61704
        • Illinois CancerCare-Bloomington
      • Canton、Illinois、美国、61520
        • Illinois CancerCare-Canton
      • Carthage、Illinois、美国、62321
        • Illinois CancerCare-Carthage
      • Centralia、Illinois、美国、62801
        • Centralia Oncology Clinic
      • Chicago、Illinois、美国、60612
        • Rush MD Anderson Cancer Center
      • Danville、Illinois、美国、61832
        • Carle at The Riverfront
      • Decatur、Illinois、美国、62526
        • Decatur Memorial Hospital
      • Decatur、Illinois、美国、62526
        • Cancer Care Specialists of Illinois - Decatur
      • Effingham、Illinois、美国、62401
        • Crossroads Cancer Center
      • Effingham、Illinois、美国、62401
        • Carle Physician Group-Effingham
      • Eureka、Illinois、美国、61530
        • Illinois CancerCare-Eureka
      • Evanston、Illinois、美国、60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Galesburg、Illinois、美国、61401
        • Illinois CancerCare-Galesburg
      • Kewanee、Illinois、美国、61443
        • Illinois CancerCare-Kewanee Clinic
      • Macomb、Illinois、美国、61455
        • Illinois CancerCare-Macomb
      • Mattoon、Illinois、美国、61938
        • Carle Physician Group-Mattoon/Charleston
      • O'Fallon、Illinois、美国、62269
        • Cancer Care Center of O'Fallon
      • Ottawa、Illinois、美国、61350
        • Illinois CancerCare-Ottawa Clinic
      • Pekin、Illinois、美国、61554
        • Illinois CancerCare-Pekin
      • Peoria、Illinois、美国、61637
        • OSF Saint Francis Medical Center
      • Peoria、Illinois、美国、61615
        • Illinois CancerCare-Peoria
      • Peru、Illinois、美国、61354
        • Illinois CancerCare-Peru
      • Princeton、Illinois、美国、61356
        • Illinois CancerCare-Princeton
      • Urbana、Illinois、美国、61801
        • Carle Cancer Center
      • Washington、Illinois、美国、61571
        • Illinois CancerCare - Washington
    • Kansas
      • Kansas City、Kansas、美国、66160
        • University of Kansas Cancer Center
      • Overland Park、Kansas、美国、66210
        • University of Kansas Cancer Center-Overland Park
      • Overland Park、Kansas、美国、66211
        • University of Kansas Hospital-Indian Creek Campus
      • Westwood、Kansas、美国、66205
        • University of Kansas Hospital-Westwood Cancer Center
      • Wichita、Kansas、美国、67214
        • Ascension Via Christi Hospitals Wichita
    • Maine
      • Portland、Maine、美国、04102
        • MaineHealth Maine Medical Center - Portland
      • Sanford、Maine、美国、04073
        • MaineHealth Cancer Care Center of York County
      • Scarborough、Maine、美国、04074
        • MaineHealth Maine Medical Center- Scarborough
      • South Portland、Maine、美国、04106
        • MaineHealth Cancer Care and IV Therapy - South Portland
    • Massachusetts
      • Worcester、Massachusetts、美国、01655
        • UMass Memorial Medical Center - University Campus
    • Missouri
      • Kansas City、Missouri、美国、64154
        • University of Kansas Cancer Center - North
      • Kansas City、Missouri、美国、64132
        • Research Medical Center
      • Lee's Summit、Missouri、美国、64064
        • University of Kansas Cancer Center - Lee's Summit
      • North Kansas City、Missouri、美国、64116
        • University of Kansas Cancer Center at North Kansas City Hospital
    • Montana
      • Great Falls、Montana、美国、59405
        • Benefis Sletten Cancer Institute
      • Kalispell、Montana、美国、59901
        • Logan Health Medical Center
    • Nevada
      • Reno、Nevada、美国、89502
        • Renown Regional Medical Center
    • New Jersey
      • Neptune City、New Jersey、美国、07753
        • Jersey Shore Medical Center
      • Summit、New Jersey、美国、07902
        • Overlook Hospital
    • New York
      • New York、New York、美国、10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Stony Brook、New York、美国、11794
        • Stony Brook University Medical Center
    • North Dakota
      • Fargo、North Dakota、美国、58122
        • Sanford Roger Maris Cancer Center
      • Fargo、North Dakota、美国、58122
        • Sanford Broadway Medical Center
    • Ohio
      • Cincinnati、Ohio、美国、45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland、Ohio、美国、44195
        • Cleveland Clinic Foundation
      • Columbus、Ohio、美国、43214
        • Riverside Methodist Hospital
      • Columbus、Ohio、美国、43210
        • Ohio State University Comprehensive Cancer Center
      • West Chester、Ohio、美国、45069
        • University of Cincinnati Cancer Center-West Chester
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Gresham、Oregon、美国、97030
        • Legacy Mount Hood Medical Center
      • Portland、Oregon、美国、97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Tualatin、Oregon、美国、97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Danville、Pennsylvania、美国、17822
        • Geisinger Medical Center
      • Lewisburg、Pennsylvania、美国、17837
        • Geisinger Medical Oncology-Lewisburg
      • Philadelphia、Pennsylvania、美国、19107
        • Thomas Jefferson University Hospital
      • Philadelphia、Pennsylvania、美国、19104
        • University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh、Pennsylvania、美国、15232
        • UPMC Hillman Cancer Center
      • Pittsburgh、Pennsylvania、美国、15232
        • UPMC-Shadyside Hospital
      • Pittsburgh、Pennsylvania、美国、15213
        • UPMC-Presbyterian Hospital
      • Pottsville、Pennsylvania、美国、17901
        • Geisinger Cancer Services-Pottsville
      • West Reading、Pennsylvania、美国、19611
        • Reading Hospital
      • Wilkes-Barre、Pennsylvania、美国、18711
        • Geisinger Wyoming Valley/Henry Cancer Center
    • South Carolina
      • Charleston、South Carolina、美国、29425
        • Medical University of South Carolina
    • South Dakota
      • Sioux Falls、South Dakota、美国、57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls、South Dakota、美国、57104
        • Sanford Cancer Center Oncology Clinic
    • Tennessee
      • Nashville、Tennessee、美国、37232
        • Vanderbilt University/Ingram Cancer Center
    • Utah
      • Salt Lake City、Utah、美国、84112
        • Huntsman Cancer Institute/University of Utah
    • Vermont
      • Burlington、Vermont、美国、05401
        • University of Vermont Medical Center
    • Virginia
      • Fairfax、Virginia、美国、22031
        • Inova Schar Cancer Institute
      • Midlothian、Virginia、美国、23114
        • Bon Secours Saint Francis Medical Center
      • Richmond、Virginia、美国、23298
        • VCU Massey Comprehensive Cancer Center
    • Washington
      • Renton、Washington、美国、98055
        • Valley Medical Center
      • Vancouver、Washington、美国、98686
        • Legacy Salmon Creek Hospital
      • Vancouver、Washington、美国、98684
        • Legacy Cancer Institute Medical Oncology and Day Treatment
    • Wisconsin
      • Antigo、Wisconsin、美国、54409
        • Aspirus Cancer Care-Antigo-Volm Cancer Center
      • Rhinelander、Wisconsin、美国、54501
        • Aspirus Cancer Care-Rhinelander-James Beck Cancer Center
      • Stevens Point、Wisconsin、美国、54481
        • Aspirus Cancer Care - Stevens Point
      • Waukesha、Wisconsin、美国、53188
        • UW Cancer Center at ProHealth Care
      • Wausau、Wisconsin、美国、54401
        • Aspirus Cancer Care-Wausau
      • Wisconsin Rapids、Wisconsin、美国、54494
        • Aspirus Cancer Care - Wisconsin Rapids

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 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
    • 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

Exclusion Criteria:

  • 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

  • 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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Non Surgical Cohort: Arm 1 - Level 1 (tocilizumab)

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 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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Tocilizumab

Given IV

其他名称：
  • 罗氏
  • 阿克泰姆拉
  • 免疫球蛋白 G1，抗（人白细胞介素 6 受体）（人-小鼠单克隆 MRA 重链），二硫化物与人-小鼠单克隆 MRA Kappa-链，二聚体
  • 互认协议
  • R-1569
  • IL-6受体单克隆抗体：托珠单抗
  • 蒂安
  • Avtozma
  • Tocilizumab-aazg
  • Tocilizumab-anoh
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗
实验性的：Non Surgical Cohort: Arm 2 - Level 2 (tocilizumab)

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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Tocilizumab

Given IV

其他名称：
  • 罗氏
  • 阿克泰姆拉
  • 免疫球蛋白 G1，抗（人白细胞介素 6 受体）（人-小鼠单克隆 MRA 重链），二硫化物与人-小鼠单克隆 MRA Kappa-链，二聚体
  • 互认协议
  • R-1569
  • IL-6受体单克隆抗体：托珠单抗
  • 蒂安
  • Avtozma
  • Tocilizumab-aazg
  • Tocilizumab-anoh
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗
实验性的：Non Surgical Cohort: Arm 4 (tocilizumab, atezolizumab)

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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Atezolizumab

Given IV

其他名称：
  • 技术中心
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
  • RG-7446
  • RG 7446
  • RO 5541267
  • RO-5541267
生物：Tocilizumab

Given IV

其他名称：
  • 罗氏
  • 阿克泰姆拉
  • 免疫球蛋白 G1，抗（人白细胞介素 6 受体）（人-小鼠单克隆 MRA 重链），二硫化物与人-小鼠单克隆 MRA Kappa-链，二聚体
  • 互认协议
  • R-1569
  • IL-6受体单克隆抗体：托珠单抗
  • 蒂安
  • Avtozma
  • Tocilizumab-aazg
  • Tocilizumab-anoh
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗
实验性的：Non Surgical Cohort:Arm 3- Level 3 (tocilizumab, atezolizumab)

Patients 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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Atezolizumab

Given IV

其他名称：
  • 技术中心
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
  • RG-7446
  • RG 7446
  • RO 5541267
  • RO-5541267
生物：Tocilizumab

Given IV

其他名称：
  • 罗氏
  • 阿克泰姆拉
  • 免疫球蛋白 G1，抗（人白细胞介素 6 受体）（人-小鼠单克隆 MRA 重链），二硫化物与人-小鼠单克隆 MRA Kappa-链，二聚体
  • 互认协议
  • R-1569
  • IL-6受体单克隆抗体：托珠单抗
  • 蒂安
  • Avtozma
  • Tocilizumab-aazg
  • Tocilizumab-anoh
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗
实验性的：Surgical Cohort: Arm A - Neoadjuvant Tocilizumab+Atezolizumab

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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Tocilizumab

Given IV

其他名称：
  • 罗氏
  • 阿克泰姆拉
  • 免疫球蛋白 G1，抗（人白细胞介素 6 受体）（人-小鼠单克隆 MRA 重链），二硫化物与人-小鼠单克隆 MRA Kappa-链，二聚体
  • 互认协议
  • R-1569
  • IL-6受体单克隆抗体：托珠单抗
  • 蒂安
  • Avtozma
  • Tocilizumab-aazg
  • Tocilizumab-anoh
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗
实验性的：Surgical Cohort: Arm B - Neoadjuvant Atezolizumab Alone

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.
程序：Conventional Surgery

Undergo surgery

程序：Magnetic Resonance Imaging

Undergo MRI

其他名称：
  • 核磁共振
  • 磁共振
  • 磁共振成像扫描
  • 医学影像、磁共振/核磁共振
  • 先生
  • 磁共振成像
  • 核磁共振成像扫描
  • 核磁共振成像
  • 磁共振成像 (MRI)
  • 磁共振成像（程序）
  • 结构核磁共振
生物：Atezolizumab

Given IV

其他名称：
  • 技术中心
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
  • RG-7446
  • RG 7446
  • RO 5541267
  • RO-5541267
程序：Biospecimen Collection

Undergo blood sample and tumor tissue collection

其他名称：
  • 生物样本采集
  • 收集的生物样本
  • 标本采集
  • 样本收集
辐射：Fractionated Stereotactic Radiation Therapy

Undergo FSRT

其他名称：
  • 分割立体定向放射治疗

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
[Non-surgical Cohort] Maximum-tolerated Dose (Safety Run-In)
大体时间：From first dose of study drug through completion of Cycle 1 (28 days).

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).
From first dose of study drug through completion of Cycle 1 (28 days).
[Non-surgical Cohort, Safety Run-In] Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
大体时间：From first dose of study drug through completion of Cycle 1 (28 days).

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.
From first dose of study drug through completion of Cycle 1 (28 days).
[Non-surgical Cohort] Objective Radiographic Response Rate (Phase II)
大体时间：Registration to 6 months

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.
Registration to 6 months

次要结果测量

结果测量
措施说明
大体时间
[Phase II Non-Surgical Cohort] Progression-free Survival
大体时间：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.

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.
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.
[Phase II Non-Surgical Cohort] Overall Survival
大体时间：From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.5 months.

Median survival time was estimated using the Kaplan-Meier method in which participants alive at last known follow-up are censored.
From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.5 months.
[Surgical Cohort] Progression-free Survival
大体时间：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.

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.
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.
[Surgical Cohort] Overall Survival
大体时间：From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.9 months.

Median survival time was estimated using the Kaplan-Meier method in which participants alive at last known follow-up are censored.
From study enrollment to death from any cause or last follow-up. Maximum follow-up time at time of analysis was 13.9 months.
Number of Participants by Highest Grade Adverse Event Reported
大体时间：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.

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.
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.

其他结果措施

结果测量
措施说明
大体时间
[Surgical Cohort] Immune Response
大体时间：Baseline and cycle 2, day 1 (1 cycle = 4 weeks)

The primary integrated correlative study is to determine the impact of anti-IL6 therapy on the GBM tumor microenvironment, and the systemic immune milieu, specifically with regard to the effect on tumor-associated macrophages, tumor-infiltrating lymphocytes, and peripheral blood immune cells. Tumor samples from patients in the window-of-opportunity surgical cohort will be obtained by surgical resection following pre-operative doses of atezolizumab and SRS with or without tocilizumab.
Baseline and cycle 2, day 1 (1 cycle = 4 weeks)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

National Cancer Institute (NCI)

合作者

NRG Oncology

调查人员

  • 首席研究员：Stephen J Bagley、NRG Oncology

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年3月11日

初级完成 (实际的)

2025年6月15日

研究完成 (估计的)

2027年8月20日

研究注册日期

首次提交

2021年1月28日

首先提交符合 QC 标准的

2021年1月28日

首次发布 (实际的)

2021年1月29日

研究记录更新

最后更新发布 (实际的)

2026年9月23日

上次提交的符合 QC 标准的更新

2026年9月22日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • NCI-2021-00410
  • U10CA180868 (美国 NIH 拨款/合同)
  • NCI-2021-00410 (注册表标识符：CTRP (Clinical Trial Reporting Program))
  • NRG-BN010 (其他标识符：CTEP)
  • NRG-BN010 (其他标识符：NRG Oncology)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

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.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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