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

Overview

About this study

The purpose of this study is to evaluate 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).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Sani Kizilbash, M.D., M.P.H.

Open for enrollment

Contact information:

Sani Kizilbash M.D., M.P.H.

(507) 293-0494

Kizilbash.Sani@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Wendy Sherman, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

La Crosse, Wis.

Mayo Clinic principal investigator

Jonathan Ticku, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Maciej Mrugala, M.D., Ph.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Eau Claire, Wis.

Mayo Clinic principal investigator

Eyad Al-Hattab, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20506806

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