Atezolizumab and Cabozantinib for the Treatment of Recurrent Glioblastoma

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Recurrent Glioblastoma, Recurrent Gliosarcoma

In brief

This phase I/II trial tests the safety and side effects of atezolizumab in combination with cabozantinib and whether they work to shrink tumors in patients with glioblastoma that has come back (recurrent). 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. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help control the disease in patients with recurrent glioblastoma.

Key facts

Study ID: NCT05039281
Run by: M.D. Anderson Cancer Center
People needed: 47
Starts: 2022-09-23
Expected to finish: 2027-12-31
Last updated by the study team: 2026-07-15

Who can join

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

You may qualify if…

Signed informed consent form (ICF)
Ability and willingness to comply with the requirements of the study protocol
Age >= 18 years
Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma). Archival tissue will be required for diagnosis confirmation. Receipt of archival tissue is not required for the start of treatment
Patients must have been previously treated with radiation and temozolomide
Patients must be at least 12 weeks out from completion of concurrent chemoradiation
Have a performance status of >= 60 on the Karnofsky performance status (KPS)
Patients at either first or second recurrence will be considered eligible
A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to study enrollment
Absolute neutrophil count (ANC) >= 1,500 /mcL
Platelets >= 100,000 /mcL
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Creatinine clearance should be calculated per institutional standard
Urine protein/creatinine ratio (UPCR) =< 1 mg/mg (=< 113.2 mg/mmol) OR 24 hour (h) urine protein =< 1g
Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X ULN
Serum albumin >= 2.8 g/dl
International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.3 X ULN
All screening labs should be performed within 14 days (+3 working days) of treatment initiation
Female subject of childbearing potential should have a negative serum pregnancy test within 14 days (+/- 3 working days) of study enrollment
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the duration of the study and 5 months after the last dose of study treatment. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
Male subjects should agree to use an adequate method of contraception during the course of the study and 5 months after the last dose of study treatment

You may not qualify if…

Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery. Prior treatment with Gliadel wafers will be excluded. Active treatment with the Optune device will be excluded
Has received radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment
Has clinically relevant ongoing complications from prior radiation therapy
Is currently participating in any other recurrent therapeutic trial after completion of chemoradiation
Has history of cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
Any serious medical condition that interferes with adherence to study procedures
Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multifocal disease. Subject has multifocal glioblastoma (GBM), defined as discrete sites of contrast enhancing disease without contiguous T2/fluid attenuated inversion recovery (FLAIR) abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted
Has history of interstitial lung disease or active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit
Contraindication for undergoing MRIs
Inability to comply with study and follow-up procedures
History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid 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
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) 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%, aclometasone 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)
Has a medical history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active pneumonitis
History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Where it is running

M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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