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

Running, not enrolling · Phase 2

Conditions studied: Diffuse Astrocytoma, IDH-Wildtype, Recurrent Glioblastoma

In brief

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.

Key facts

Study ID

NCT04729959

Run by

National Cancer Institute (NCI)

People needed

61

Starts

2022-03-11

Expected to finish

2026-09-04

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• 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)

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
• 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)

Where it is running

• Valley Medical Center — Renton, Washington, United States
• Legacy Cancer Institute Medical Oncology and Day Treatment — Vancouver, Washington, United States
• Legacy Salmon Creek Hospital — Vancouver, Washington, United States
• Langlade Hospital and Cancer Center — Antigo, Wisconsin, United States
• Aspirus Cancer Care - James Beck Cancer Center — Rhinelander, Wisconsin, United States
• Aspirus Cancer Care - Stevens Point — Stevens Point, Wisconsin, United States
• UW Cancer Center at ProHealth Care — Waukesha, Wisconsin, United States
• Aspirus Regional Cancer Center — Wausau, Wisconsin, United States
• Aspirus Cancer Care - Wisconsin Rapids — Wisconsin Rapids, Wisconsin, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• Kaiser Permanente-Bellflower — Bellflower, California, United States
• Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• Kaiser Permanente-Ontario — Ontario, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Roseville — Roseville, California, United States
• Sutter Roseville Medical Center — Roseville, California, United States
• Sutter Medical Center Sacramento — Sacramento, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Kaiser Permanente-San Diego Zion — San Diego, California, United States
• California Pacific Medical Center-Pacific Campus — San Francisco, California, United States
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States
• UCHealth Memorial Hospital Central — Colorado Springs, Colorado, United States
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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