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Cancer

Recruiting

Baptist Health Louisville

Arvinda Padmanabhan

Principal Investigator

Kelly Strange

Baptist Health Lexington

Arvinda Padmanabhan

Principal Investigator

Elizabeth Rush

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Overview

A071702: A Phase II Study of Checkpoint Blockade Immunotherapy in Patients with Somatically Hypermutated Recurrent Glioblastoma
Description

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).

Eligibility Criteria

Inclusion

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 bidimensional 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

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