Study of Sonodynamic Therapy in Participants with Recurrent High-Grade Glioma

NCT04559685 | Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 2020-1121-500-032-34-38
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 0 single center, first in human, open-label study of ascending energy doses of sonodynamic therapy (SDT) utilizing the MRgFUS combined with intravenous ALA to assess safety and efficacy in up to 45 participants with recurrent HGG. Eligible participants who are scheduled for resection will be administered intravenous (IV) aminolevulinic acid HCl (ALA) approximately six to seven (6-7) hours prior to receiving sonodynamic therapy (SDT).

Conditions

High Grade Glioma

Outcome Measures

Primary Outcomes (2)

• Biological changes associated with the sonodynamic therapy

  The percentage (%) of Cleaved Caspase-3 of the surgical tissue will be quantified and compared to intra-patient control specimens.

  Intraoperatively 4, 7, or 14 days post sonodynamic therapy

• Radiographic evidence of tumor physiological imaging changes associated with SDT in recurrent HGG patients (Arm E)

  Volume of enhancing tumor will quantified and compared between pre and post procedural scans (Arm E)

  Intraoperatively 4, 7, or 14 days post sonodynamic therapy

Secondary Outcomes (12)

• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy

  Pre and 14 Days Post-operative scan

• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy

  Pre and 14 Days Post-operative scan

• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy

  Pre and 14 Days Post-operative scan

• To identify oxidative stress in tissue exposed to sonodynamic therapy in recurrent high-grade glioma patients.

  Intraoperatively 2, 4, or 6 days post sonodynamic therapy

• Performance of MRgFUS

  Day 1

Study Arms (5)

Arm A Energy Dose-escalation

EXPERIMENTAL

In Arm A, the dose-escalation cohort, there will be 3 cohorts of ascending MRgFUS power/energy dose combinations with a fixed SONALA-001 dose and fixed surgical time. Arm A will determine the power/energy dose combination for Arm B.

Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Arm B Time-escalation

EXPERIMENTAL

In Arm B, the time-escalation cohort, the SONALA-001 and power/energy dose combination will be fixed. Participants will be enrolled into two time cohorts (2 days and 6 days post-SDT).

Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Arm C ALA Dose-escalation

EXPERIMENTAL

In Arm C, the MRgFUS power/energy dose will be fixed based on Arm A MTD/OBD, with the SONALA-001 dose escalation.

Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Arm D MRgFUS alone

EXPERIMENTAL

In Arm D, MRgFUS treatment alone will be given at the optimal energy determined from previous Arms.

Device: MR-Guided Focused Ultrasound device (MRgFUS)

Arm E Optimal energy and ALA dose

EXPERIMENTAL

In Arm E patients will receive treatment at the optimal energy and ALA dose determined form prior Arms.

Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Interventions

SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS) COMBINATION_PRODUCT

SONALA-001(ALA) given 5-7 hours prior to receiving the MRgFUS.

Arm A Energy Dose-escalation; Arm B Time-escalation; Arm C ALA Dose-escalation; Arm E Optimal energy and ALA dose

MR-Guided Focused Ultrasound device (MRgFUS) DEVICE

MR-Guided Focused Ultrasound device (MRgFUS) alone

Arm D MRgFUS alone

Eligibility Criteria

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

You may qualify if:

• Arms A-D: Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as participants who have progressed on or following standard therapy as determined by the investigator. Arm E: Participant at first recurrence with an unmethylated HGG, has completed standard therapy and is not currently scheduled for resection.
• Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI with positive perfusion.
• Arms A-D (only): Have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with a volume of at least 6 cm3 and ≤ 20cm3 of targeted treatment area.
• Age ≥18 at time of consent.
• Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982).
• Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility)
• Adequate bone marrow function:
• absolute neutrophil count ≥1,000/mcL
• Platelets (at time of surgery) ≥100,000/mcL
• hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.
• Adequate hepatic and renal function:
• total bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• AST(SGOT) ≤3 X institutional ULN
• ALT(SGPT) ≤3 X institutional ULN
• GGT ≤3 X institutional ULN

You may not qualify if:

• Known active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Have had a recent (≤3 months prior to first dose of study drug) transient ischemic attack or stroke.
• Significant vascular disease (e.g. aortic aneurysm)
• Evidence of bleeding diathesis or coagulopathy
• Diagnosis of porphyria
• Unstable angina and/or congestive heart failure within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Serious and inadequately controlled cardiac arrhythmia
• Acute exacerbation of chronic obstructive pulmonary disease
• Inability to undergo MRI (e.g., presence of a pacemaker)
• Pregnancy or breastfeeding
• Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
• Hypersensitivity against porphyrins
• Treatment with another investigational drug within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.

Sponsors & Collaborators

• Nader Sanai: lead
• Barrow Neurological Institute: collaborator
• Ivy Brain Tumor Center: collaborator
• SonALAsense, Inc.: collaborator
• InSightec: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Nader Sanai, MD

  St. Joseph's Hospital and Medical Center, Phoenix

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phase 0 Navigator

CONTACT

602-406-8605; research@ivybraintumorcenter.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Ivy Brain Tumor Center

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 23, 2020
• Study Start: March 15, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)