Atezolizumab in Combination With Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

NCT03174197 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2016-0867NCI-2018-02629
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and how well atezolizumab works in combination with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma. 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. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. It is not yet known how well atezolizumab works in combination with temozolomide and radiation therapy in treating patients with glioblastoma.

Conditions

Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicities (DLTs) (Phase I)

  Will monitor time to DLT continuously using a Bayesian method that assumes the median time to DLT follows an Inverse gamma distribution and that the individual times to DLT follow an exponential distribution.

  Up to 10 weeks

• Overall survival (OS) (Phase II)

  Kaplan-Meier curves will be generated for OS and median times and probabilities estimated with 95% confidence intervals.

  Up to 3 years

• Incidence of adverse events

  The overall toxicity rate will be estimated with exact binomial 95% confidence intervals. Adverse Events will be tabulated by grade and by their relationship to the treatment.

  Up to 3 years

Secondary Outcomes (3)

• Overall response rate

  Up to 3 years

• Duration of response (DoR)

  Up to 3 years

• Progression-free survival (PFS)

  Up to 3 years

Study Arms (2)

Adjuvant phase (temozolomide, atezolizumab)

EXPERIMENTAL

Patients receive temozolomide PO on days 1-5 and atezolizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Temozolomide

Concurrent phase (temozolomide, atezolizumab, RT)

EXPERIMENTAL

Patients receive temozolomide PO daily on days 1-42 and atezolizumab IV over 30-60 minutes on day 1, 15, 29, and 42. Patients undergo RT 5 days per week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Radiation: Radiation Therapy; Drug: Temozolomide

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Adjuvant phase (temozolomide, atezolizumab); Concurrent phase (temozolomide, atezolizumab, RT)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Concurrent phase (temozolomide, atezolizumab, RT)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Adjuvant phase (temozolomide, atezolizumab); Concurrent phase (temozolomide, atezolizumab, RT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF).
• Ability and willingness to comply with the requirements of the study protocol.
• 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 undergone surgery and must not have had any further treatment following surgery.
• Have a performance status of \>= 60 on the Karnofsky performance status (KPS).
• A baseline brain magnetic resonance imaging (MRI) obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids no greater than 4 mg a day of dexamethasone for at least 5 days.
• Patients must start treatment within 6 weeks of definitive resection.
• Absolute neutrophil count (ANC) \>= 1,500 /mcL.
• Platelets \>= 100,000 /mcL.
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L.
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 x upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN.
• 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 glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN.
• International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) \</=1.5 x ULN.
• All screening labs should be performed within 14 days (+ 3 working days) of treatment initiation.

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. Prior treatment with the Optune device will be excluded.
• Is currently participating or has participated in any other newly diagnosed therapeutic trial before or after chemoradiation.
• Any serious medical condition that interferes with adherence to study procedures.
• Patients may not receive concomitant chemotherapy, hormonal therapy, immunotherapy, or radiotherapy while patients are on study.
• 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 evidence 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, Sjögren's syndrome, Bell's palsy, Guillain-Barré 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%, flucinolone 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).
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

atezolizumab; Radiotherapy; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shiao-Pei S Weathers

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 2, 2017
• Study Start: June 30, 2017
• Primary Completion: September 17, 2025
• Study Completion: September 17, 2025
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

US (1)