Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma

• Status: Terminated
• Trial end date: 2021-03-10
• Target enrollment: 0
• Participant gender: All

Summary

Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baptist Health South Florida
• Collaborators: Bristol-Myers Squibb; NovoCure Ltd.
• Treatments: Antibodies, Monoclonal; Bevacizumab; Ipilimumab; Nivolumab

Criteria

Inclusion Criteria:

• Histologically confirmed World Health Organization Grade IV glioblastoma with supratentorial distribution.

• Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by RANO criteria, or documented recurrent glioblastoma on biopsy.

• Prior therapies including radiation and temozolomide.

• Only 1-2 prior treatments for recurrences are allowed. Resection of recurrent glioblastoma is not considered a prior treatment.

• Must be at least 12 weeks from radiotherapy or progression outside of the high-dose radiation target volume or unequivocal evidence of progressive tumor on biopsy.

• All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.

• Karnofsky Performance Status (KPS) ≥ 60

• Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:

• absolute neutrophil count ≥ 1,000/mcL

• platelets ≥ 100,000/mcL

• hemoglobin > 8.0 mg/dL

• total bilirubin ≤ 2.0 x upper limit of normal

• AST (SGOT)/ALT (SGPT) ≤2.5 × upper limit of normal

• creatinine or creatinine clearance ≥60 mL/min/1.73 m2 for creatinine >ULN

• Corticosteroid dose must be stable or decreasing for at least 5 days prior to enrollment.

• Ability to understand and the willingness to provide written informed consent.

Exclusion Criteria:

• Infratentorial disease.

• Prior use of bevacizumab, ipilimumab or other CTLA-4 inhibitor, or TTFields.

• Tumors with known IDH1 or IDH2 mutations.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.

• Current or planned participation in a study of an investigational agent or using an investigational device.

• Uncontrolled intercurrent illness that would limit compliance with study requirements.

• Active or life-threatening infection requiring intravenous or >2 weeks of systemic therapy.

• Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy requires a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis unless the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site.

• breastfeeding must be discontinued by enrollment on study.

• Uncontrolled HIV or AIDS is not allowed. Patients with known history of HIV but with undetectable viral load on antiretroviral therapy are allowed.

• CHF, or MI or hemorrhagic/ischemic stroke in the last 3 months.

• Active illicit drug use or diagnosis of alcoholism

• Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.

• Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of start of treatment.

• Any significant autoimmune disorders expected to impact multiple or internal organs, excluding mild eczema or autoimmune thyroiditis treated with thyroidectomy and requiring systemic immunosuppressive or immunomodulatory therapy.

• Any implanted programmable cranial device, including reprogrammable ventriculoperitoneal shunt (VPS) or cochlear implants, that precludes use of TTFields (Optune) therapy.