OPTIMUS PRIME: Safety and Feasibility of OPTune GIO® Integrated With MRI-gUided Laser Ablation Surgery and Pembrolizumab for Recurrent GlIoblastoMa, A randomizEd Trial

NCT06558214 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB202400948OCR45231
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this study we are evaluating the safety and feasibility of the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent or progressive glioblastoma (GBM) WHO Grade IV, IDH wild type or recurrent or progressive astrocytoma WHO grade IV.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Number of participants experiencing a DLT after receiving the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent glioblastoma from both arms

  Patients who receive the combinatorial regimen will get the ongoing safety assessment with DLT \</= 33% treated subjects

  baseline up to 3 months

• Percentage of participants treated with the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent glioblastoma from both arms

  Feasibility is defined as the ability to successfully deliver the combinatorial treatment of MLA, optune GIO® and pembrolizumab to at least 67% of enrolled subjects who undergo MLA.

  baseline up to 3 months

Study Arms (2)

Arm 1: Optune GIO® pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA

EXPERIMENTAL

Patients randomized to treatment arm 1 will start treatment with Optune GIO® for 3-7 days and undergo MLA and biopsy for tumor diagnosis and immune monitoring. Treatment with Optune GIO® will be paused prior to the MLA procedure until at least 10 days post MLA. Patients will then resume treatment with Optune GIO® and receive pembrolizumab 200 mg IV every 3 weeks (+/- 4 days) starting no sooner than 1 week after the start of Optune GIO®.

Drug: Pembrolizumab; Device: Optune GIO®; Device: NeuroBlate®

Arm 2: Optune GIO®+Pembrolizumab pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA

EXPERIMENTAL

Patients randomized to treatment arm 2, will start treatment with Optune GIO® for 3-10 days and receive one infusion of pembrolizumab before undergoing MLA/biopsy. Patients will resume Optune GIO® no earlier than 10 days post-surgery and receive pembrolizumab 200 mg IV every 3 weeks (+/- 4 days) starting no sooner than 1 week after the start of Optune GIO®.

Drug: Pembrolizumab; Device: Optune GIO®; Device: NeuroBlate®

Interventions

Pembrolizumab DRUG

Keytruda® is the trade name for pembrolizumab, which will be given as 200mg IV Q3 weeks. This treatment will continue for up to two years.

Also known as: Keytruda

Arm 1: Optune GIO® pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA; Arm 2: Optune GIO®+Pembrolizumab pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA

Optune GIO® DEVICE

. . Optune GIO® TTFields treatment will begin 3-7 days prior to MLA for Arm1 and 3-10 days prior to MLA for Arm 2.

Also known as: TTFields

Arm 1: Optune GIO® pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA; Arm 2: Optune GIO®+Pembrolizumab pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA

NeuroBlate® DEVICE

Treatment with NeuroBlate will occur one time at the beginning of the study.

Also known as: MLA, LITT

Arm 1: Optune GIO® pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA; Arm 2: Optune GIO®+Pembrolizumab pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be at least 18 years of age.
• Diagnosis of recurrent or progressive glioblastoma, WHO Grade IV, IDH wild-Type or astrocytoma WHO grade IV.
• Unequivocal evidence of tumor progression by brain MRI scan per RANO criteria. Patients who experience a second disease progression are eligible provided that they have not been previously treated with anti-angiogenic agents including bevacizumab (at the exception of bevacizumab radiation necrotic protocol)
• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 28 days prior to study enrollment.
• There must be an interval of at least 12 weeks from the completion of radiation therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks but more than 4 weeks from the completion of radiotherapy, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.
• Karnofsky performance status (KPS) ≥60%.
• Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to MLA is allowed per standard of care but is not required.
• Candidate for Optune GIO® therapy.
• Candidate for pembrolizumab.
• Adequate bone marrow and organ function as defined below:
• ANC ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)
• Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN
• Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN

You may not qualify if:

• Prior treatment with any anti-angiogenic agent, including bevacizumab.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Prior treatment with a monoclonal antibody within 4 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the projected first dose of pembrolizumab or has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: patients with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Presence of infratentorial lesions, brainstem lesions, or lesions that are less than 5 mm from the hypophysis or cranial nerves.
• Multifocal gliomas that are bilateral. Patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single MLA procedure. Also note that corpus callosal tumors are eligible even if they are bilateral as long as they satisfy the size and shape limits of MLA as determined by the performing neurosurgeon.
• Presence of leptomeningeal metastases beyond the cranial vault. (Focal leptomeningeal enhancement allowable at the discretion of the principal investigator).
• Requires corticosteroids equivalent to \> 4mg dexamethasone daily.
• Recent (within 8 weeks) history of CNS hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during MLA.
• Requires therapeutic doses of anticoagulants unless anticoagulation can be safely discontinued per standard practice (e.g. first DVT for which anticoagulation has been at least 3 months and repeat imaging demonstrates resolution of DVT) or an IVC filter can be used in place of anticoagulation.
• Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of MLA treatment.
• Received a live vaccine within 30 days prior to the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2).
• Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 3 weeks of the projected initiation of study treatment (Optune GIO® for Arm 1 and LITT for Arm 2).
• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 4 mg).

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Ashley Ghiaseddin, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victoria Hope

CONTACT

352-273-9000; victoria.hope@neurosurgery.ufl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 16, 2024
• Study Start: December 10, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (1)