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

A Phase I/II Trial of Combination Tumor Treating Fields, Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: Nivolumab 240 mg IV; Device: NovoTTF200A (Optune); Drug: Nivolumab 3 mg/kg; Drug: Ipilimumab 1 mg/kg

Detailed Description

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.

The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months.

Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab Monotherapy; Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months	Drug: Nivolumab 240 mg IV; Nivolumab IV 240mg IV every 2 weeks for maximum of 24 months.; Other Names: Nivolumab Monotherapy; Device: NovoTTF200A (Optune); A device to be worn continuously for a goal of 75% of the time, ranging from 18 hours daily nonstop or 22 hours daily with 2-3 days off monthly.
Experimental: Nivolumab+Ipilimumab; Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months	Drug: Nivolumab 240 mg IV; Nivolumab IV 240mg IV every 2 weeks for maximum of 24 months.; Other Names: Nivolumab Monotherapy; Device: NovoTTF200A (Optune); A device to be worn continuously for a goal of 75% of the time, ranging from 18 hours daily nonstop or 22 hours daily with 2-3 days off monthly.; Drug: Nivolumab 3 mg/kg; Nivolumab IV 3mg/kg every 2 weeks for maximum of 24 months.; Other Names: Nivolumab+Ipilimumab; Drug: Ipilimumab 1 mg/kg; Ipilimumab IV 1 mg/kg every 6 weeks for maximum of 4 doses.; Other Names: Nivolumab+Ipilimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate according to modified iRANO criteria	Overall response rate is the proportion of patients whose best overall response per modified iRANO criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy	Analyses will occur 4 months after accrual of 15 patients for each arm.

Collaborators and Investigators

• Sponsor: Baptist Health South Florida
• Collaborators: Bristol-Myers Squibb; NovoCure Ltd.
• Investigators: Principal Investigator: Yazmin Odia, Miami Cancer Institute at Baptist Health, Inc.

Publications and helpful links

Helpful Links

• Miami Cancer Institute Website

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 29, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: recurrent glioblastoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: 2017-ODI-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No