Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma

Conditions

• Gliosarcoma
• MGMT-Unmethylated Glioblastoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Contrast-enhanced Magnetic Resonance Imaging — PROCEDURE
  Undergo contrast-enhanced brain MRI
• Ipilimumab — BIOLOGICAL
  Given IV
• Nivolumab — BIOLOGICAL
  Given IV
• NovoTTF-100A Device — DEVICE
  Wear Optune device
• Quality-of-Life Assessment — OTHER
  Ancillary studies
• Questionnaire Administration — OTHER
  Ancillary studies
• Radiation Therapy — RADIATION
  Undergo radiation therapy
• Temozolomide — DRUG
  Given PO

Study Details

This phase II/III trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy in combination with immunotherapy with ipilimumab and nivolumab in treating patients with newly diagnosed MGMT unmethylated glioblastoma. Radiation therapy uses high energy photons to kill tumor and shrink tumors. Chemotherapy drugs, 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. Temozolomide, may not work as well for the treatment of tumors that have the unmethylated MGMT. Immunotherapy with monoclonal antibodies called immune checkpoint inhibitors, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is possible that immune checkpoint inhibitors may work better at time of first diagnosis as opposed to when tumor comes back. Giving radiation therapy with ipilimumab and nivolumab may lengthen the time without brain tumor returning or growing and may extend patients' life compared to usual treatment with radiation therapy and temozolomide.

Key Dates

Start date

Sep 1, 2020

Status verified

Apr 2026

Primary completion

Jan 13, 2023

Completion

Dec 23, 2025

Study Design

Enrollment

159 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm I (radiation therapy, temozolomide)
  Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.
• Experimental: Arm II (radiation therapy, ipilimumab, nivolumab)
  Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.

Primary Outcome Measure

Progression-free Survival (PFS) (Phase II) [ Time Frame: From randomization to date of progression, death, or last known follow-up, whichever occurs first. Maximum follow-up time was 19.3 months. ]

Locations (285)

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