Randomized Study of Neo-adjuvant and Adjuvant Pembrolizumab With and Without Targeted Blood Brain Barrier Opening Using Exablate MRI-guided Focused Ultrasound (Exablate MRgFUS) for Recurrent Glioblastoma

NCT05879120 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0812NCI-2023-04164
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the Exablate Model 4000 Type 2 ("Exablate System") with the DEFINITY® ultrasound contrast agent can temporarily disrupt the blood brain barrier in patients with recurrent (has grown back) glioblastoma who are scheduled to receive pembrolizumab.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (2)

Neoadjuvant pembrolizumab

EXPERIMENTAL

Drug: Pembrolizumab

Exablate MRgFUS + neoadjuvant pembolizumab

EXPERIMENTAL

Device: Exablate MRgFUS + neoadjuvant pembolizumab

Interventions

Pembrolizumab DRUG

Given by IV (vein)

Also known as: Keytruda, MK-3475, SCH-900475

Neoadjuvant pembrolizumab

Exablate MRgFUS + neoadjuvant pembolizumab DEVICE

Given by IV (vein)

Exablate MRgFUS + neoadjuvant pembolizumab

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of World Health Organization Grade IV glioma (glioblastoma or gliosarcoma) with first recurrence of disease will be enrolled in this study.
• Only patients with confirmed IDH wild-type glioma will be enrolled in this study.
• Participants must have undergone prior surgery and completed standard of care treatment with concurrent temozolomide and radiation therapy.
• Patient is a surgical candidate and resection is indicated as standard of care. Tumor must be supratentorial for surgical candidacy.
• Surgery is expected to achieve 60% or greater resection of enhancing tumor.
• A male participant must agree to use a contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 30 days (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 150 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have unequivocal tumor progression and measurable disease based on mRANO criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or biopsy specimen of a tumor not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Receipt of archival tissue is not required for the start of treatment.
• Have a Karnofsky Performance Score (KPS) of ≥ 70 at the time of enrollment. Evaluaton of KPS is to be performed within 7 days prior to the first dose of study intervention.The participant is on a stable or decreasing dose of steroids of less than or equal to 2 mg dexamethasone per day.
• Have adequate organ function as defined in the following table (Table 3). Specimens must be collected within 7-14 days prior to the start of study intervention.
• System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥100 000/µL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization and each dose of the study treatment. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of the study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving the study medication. (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
• Has received prior systemic anti-VEGF or anti-VEGFR treatment (e.g. bevacizumab, cedirinab, aflibercept, vandertanib, XL-184, sunitinib, etc.)
• Has received prior radiotherapy within 12 weeks of start of study intervention unless there is histologically proven tumor recurrence. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received temozolomide within 4 weeks, lomustine within 6 weeks, or any non-cytotoxic tumor directed therapy within 5 half-lives or 2 weeks of start of study intervention.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Treatment with systemic immunostimulatory agents (including but not limited to interferon \[IFN\] or interleukin \[IL\]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
• Patient's glioblastoma meets criteria to be defined as multifocal or multicentric.
• Subjects presenting with the following imaging characteristics
• Evidence of acute intracranial hemorrhage.
• Containing calcifications in the focused ultrasound sonication beam path in the event system tools cannot tailor the treatment around these calcification spots
• Evidence of \>2 mm midline shift evidence of subfalcine, uncal, or tonsillar herniation on pre-operative imaging

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• InSightec: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

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

• Vinay Puduvalli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: May 30, 2023
• Study Start: July 30, 2024
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

US (1)