A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden

Running, not enrolling · Phase 2

Conditions studied: Astrocytoma, IDH-Mutant, Grade 4, Diffuse Glioma, Glioblastoma, IDH-Wildtype, Secondary Glioblastoma

In brief

This phase II trial studies the effect of immunotherapy drugs (ipilimumab and nivolumab) in treating patients with glioma that has come back (recurrent) and carries a high number of mutations (mutational burden). Cancer is caused by changes (mutations) to genes that control the way cells function. Tumors with high number of mutations may respond well to immunotherapy. Immunotherapy with monoclonal antibodies 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. Giving ipilimumab and nivolumab may lower the chance of recurrent glioblastoma with high number of mutations from growing or spreading compared to usual care (surgery or chemotherapy).

Key facts

Study ID

NCT04145115

Run by

National Cancer Institute (NCI)

People needed

37

Starts

2020-12-24

Expected to finish

2026-12-31

Last updated by the study team

2026-08-04

Who can join

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

You may qualify if…

• PRE-REGISTRATION ELIGIBILITY CRITERIA:
• Histologically confirmed glioblastoma (World Health Organization [WHO] grade IV) presenting at first or second recurrence including secondary glioblastoma
• Glioblastoma IDH-wildtype central nervous system (CNS) WHO grade 4
• Diffuse, astrocytic glioma IDH-wildtype with one or more of the following histological or genetic features: microvascular proliferation, necrosis, TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes
• Astrocytoma, IDH-mutant CNS WHO grade 4
• Diffuse astrocytic glioma IDH-mutant (with frequent ATRX and/or TP53 mutation and absence of 1p/19q codeletion), with necrosis and/or microvascular proliferation or one with lower grade histological features displaying homozygous deletion of CDKN2A and/or CDKN2B
• NOTE: The eligibility criteria were changed to include the new diagnostic language from the WHO 2021 pathology classification change. The above diagnoses therefore reflect the change and include the entities that were previously eligible but now carry updated pathologic classification
• Presence of measurable disease, as defined by a bidimensionally measurable lesion on magnetic resonance imaging (MRI) with a minimum diameter of 10 mm in both dimensions, prior to resection or biopsy of recurrent tumor
• Tissue available from surgical resection or biopsy of recurrent tumor =< 28 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor =< 28 days after pre-registration
• Does not require > 4 mg dexamethasone beyond the perioperative period defined as the time =< 2 weeks after surgical procedure
• No active autoimmune disease or history of autoimmune disease
• These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• No prior treatment with checkpoint blockade therapies (anti-CTLA4, anti-PD1/PD-L1) or bevacizumab
• No prior treatment with laser ablation at the time of recurrent tumor tissue sampling. Patients who have previously undergone laser ablation >= 4 months prior to recurrent tumor tissue sampling can be included
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Able to undergo brain MRI with contrast
• Absolute neutrophil count >= 1500/mm\^3
• Platelet count >= 100,000/mm\^3
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• If Gilbert syndrome, then total bilirubin =< 3 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.0 x ULN
• Creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula)
• History of active malignancy (outside of the patient's glioblastoma) that has required treatment within the previous 2 years. Participant with prior history of in situ cancer or basal or squamous cell skin cancer are eligible

Where it is running

• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States
• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Mercy Cancer Center - Carmichael — Carmichael, California, United States
• Mercy San Juan Medical Center — Carmichael, California, United States
• Mercy Cancer Center - Elk Grove — Elk Grove, California, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• Mercy Cancer Center - Rocklin — Rocklin, California, United States
• Mercy Cancer Center - Sacramento — Sacramento, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Pacific Central Coast Health Center-San Luis Obispo — San Luis Obispo, California, United States
• Mission Hope Medical Oncology - Santa Maria — Santa Maria, California, United States
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.