Sonodynamic Therapy in Patients With Recurrent GBM

NCT06039709 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: HSR230064
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This pilot study will evaluate the safety and feasibility of combining an investigational drug called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial approach is called sonodynamic therapy (SDT), and this investigational therapy is being tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for recurrent GBM.

Conditions

Recurrent Glioblastoma; Glioblastoma Multiforme; GBM

Keywords

Sonodynamic Therapy; Low-Intensity Focused Ultrasound (LIFU); Focused Ultrasound; 5-ALA; Brain Cancer

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  Per NCI Common Terminology Criteria for Adverse Events v5.0

  From informed consent through 30 days after study intervention is complete

• Severity of adverse events

  Per NCI Common Terminology Criteria for Adverse Events v5.0

  From informed consent through 30 days after study intervention is complete

• Incidence of intracranial hemorrhage and/or worsening of edema

  On post-SDT MRIs

  From day after SDT (day 1) up to the time of surgery (day 7-day 21)

• Extent of targeted tumor area receiving FUS

  Use of NaviFUS system to target a maximum of 50% of the tumor volume of one contiguous lesion

  Day 0

• Ability to have participants undergo planned surgery without delay

  A delay is defined as more than 3 weeks after SDT

  within 3 weeks following SDT

Secondary Outcomes (2)

• Response of target tissue following SDT on imaging

  From day after SDT (day 1) up to 100 days after intervention is completed

• Histologic tumor devitalization

  Day 7-Day 21

Study Arms (1)

Sonodynamic Therapy (5-ALA + LIFU)

EXPERIMENTAL

Administration of SDT occurs 1-3 weeks prior to GBM resection

Combination Product: 5-ALA and Low-Intensity Focused Ultrasound (SDT)

Interventions

5-ALA and Low-Intensity Focused Ultrasound (SDT) COMBINATION_PRODUCT

5-ALA (20mg/kg orally) given \~6 hours prior to LIFU. Focused ultrasound will target a maximum of 50% of the tumor.

Sonodynamic Therapy (5-ALA + LIFU)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease status and Disease Parameters:
• Suspected recurrent glioblastoma that is clearly measurable based on the modified Response Assessment in Neuro-Oncology (RANO) criteria
• The tumor lesion needs to comprise at least 1 contrast-enhancing lesion with a volume of ≥ 2 cm3 and ≤ 20 cm3 of targeted treatment area
• Tumor tissue to be treated is in a surgically accessible brain region for resection
• The brain tumor to be treated must be in the treatment envelope of the NaviFUS system (30 mm to 90 mm from the inner skull table)
• Recurrence will be assessed by imaging and confirmed by consensus at tumor board
• Men or women between the ages of 18-80 years of age at the time of consent
• No contraindication to repeat brain surgery
• Karnofsky Performance Score of 70-100
• Able to undergo an MRI with contrast
• Able to swallow oral medications
• Willingness and ability to comply with scheduled visits, treatment plans, lifestyle considerations, laboratory tests, and other procedures.
• Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
• Participants who received prior chemotherapy, radiation therapy, immunotherapy, and/or another investigational therapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1 or baseline) from the acute effects of the therapy or therapies) except for residual alopecia or Grade 2 peripheral neuropathy prior to registration.
• Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):

You may not qualify if:

• Known sensitivity or allergy to 5-ALA
• Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
• Diagnosis of porphyria
• Hypersensitivity against porphyrins
• Pregnancy
• Significant cardiac disease or coagulopathy
• Herniation / intractable seizure / other clinical indications requiring urgent resection
• 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)
• Have had a recent (≤3 months prior to registration) transient ischemic attack or stroke
• Significant vascular disease (e.g. aortic aneurysm)
• Evidence of bleeding diathesis or coagulopathy
• Need for systemic anticoagulation which cannot be held for 7 days prior to SDT
• Unstable angina and/or congestive heart failure (NYH Class III or Class IV; see section 13.2) within 6 months prior to registration
• Severe hypertension (systolic ≥ 180 mm Hg; diastolic ≥ 120 mm Hg) despite anti-hypertensive medications
• Transmural myocardial infarction within 6 months prior to registration

Sponsors & Collaborators

• Shayan Moosa, MD: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Shayan Moosa, MD

  UVA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachary Sturgill

CONTACT

434-243-9986; FFM7RC@uvahealth.org

Judith Beenhakker, M.S.

CONTACT

434-982-1856; jgb3p@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurosurgery

Study Record Dates

• First Submitted: September 10, 2023
• First Posted: September 15, 2023
• Study Start: January 31, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)