Anchorage, Alaska 99508

  • Secondary Glioblastoma

Purpose:

This phase II trial studies the effect of immunotherapy drugs (ipilimumab and nivolumab) in treating patients with glioblastoma that has come back (recurrent) and carries a high number of mutations. 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).


Study summary:

PRIMARY OBJECTIVE: I. To determine whether the combination of ipilimumab and nivolumab increases the tumor response rate assessed by modified Response Assessment in Neuro-Oncology (RANO) Criteria in patients with hypermutated recurrent glioblastoma. SECONDARY OBJECTIVES: I. Estimate the overall survival distribution, median survival, and one-year survival rate of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. II. Estimate the progression-free survival distribution and median progression-free survival of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. III. Determine the adverse event profile of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. EXPLORATORY OBJECTIVES: I. Test whether PD-L1 or immunologic infiltrate in the tumor microenvironment are associated with objective tumor response, overall survival, progression-free survival, tumor mutational burden, or rates of grade 3 or higher adverse events. II. Test whether MGMT status, microsatellite instability (MSI) status, mutational signatures, or amount of tumor mutational burden (TMB) including germline analysis are associated with objective tumor response, overall survival, progression-free survival, or rates of grade 3 or higher adverse events. III. Evaluate associations between exome and transcriptome gene levels with objective tumor response, overall survival, progression-free survival, rates of grade 3 or higher adverse events. IV. Evaluate associations between the gut microbiome and objective tumor response. V. Response rate using immunotherapy (i)RANO. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients without disease progression are followed every 8 weeks until disease progression, then every 3 months for up to 3 years. Patients with disease progression after completion of study treatment are followed every 3 months for up to 3 years.


Criteria:

Inclusion Criteria: - PRE-REGISTRATION: - Histologically confirmed glioblastoma (World Health Organization [WHO] grade IV) presenting at first or second recurrence including secondary glioblastoma - 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 =< 14 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor =< 14 days after pre-registration - Does not require > 4 mg dexamethasone beyond the perioperative period defined as the time =< 2 weeks after surgical procedure - 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) - REGISTRATION: - Tissue obtained from biopsy or resection at first or second recurrence exhibits TMB >= 20 on FoundationOne CDx testing Exclusion Criteria: - 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


NCT ID:

NCT04145115


Primary Contact:

Principal Investigator
Gavin P Dunn
Alliance for Clinical Trials in Oncology


Backup Contact:

N/A


Location Contact:

Anchorage, Alaska 99508
United States

Site Public Contact
Phone: 907-212-6871
Email: AKPAMC.OncologyResearchSupport@providence.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: September 19, 2021

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