GBM 001: Sonodynamic Therapy in Patients With Recurrent GBM

Sponsor

Shayan Moosa, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06039709

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Glioblastoma Glioblastoma Multiforme GBM	Combination Product: 5-ALA and Low-Intensity Focused Ultrasound (SDT)	Phase 1

Detailed Description

The combination of 5-ALA (Gleolan) and LIFU is collectively known as sonodynamic therapy (SDT). SDT is an investigational therapy that will be administered 1-3 weeks before surgery for recurrent GBM. Researchers seek to determine the safety and feasibility of this therapy as well as measure its effectiveness to elicit tumor-cell death. All participants are expected to stay overnight in the hospital following administration of SDT to monitor for adverse events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Sonodynamic Therapy With 5-ALA for the Treatment of Recurrent Glioblastoma Using Neuronavigation-Guided Low-Intensity Focused Ultrasound

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

May 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sonodynamic Therapy (5-ALA + LIFU) Administration of SDT occurs 1-3 weeks prior to GBM resection	Combination Product: 5-ALA and Low-Intensity Focused Ultrasound (SDT) 5-ALA (20mg/kg orally) given ~6 hours prior to LIFU. Focused ultrasound will target a maximum of 50% of the tumor.

Arm

Intervention/Treatment

Experimental: Sonodynamic Therapy (5-ALA + LIFU)

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

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

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

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [From informed consent through 30 days after study intervention is complete]
Per NCI Common Terminology Criteria for Adverse Events v5.0
Severity of adverse events [From informed consent through 30 days after study intervention is complete]
Per NCI Common Terminology Criteria for Adverse Events v5.0
Incidence of intracranial hemorrhage and/or worsening of edema [From day after SDT (day 1) up to the time of surgery (day 7-day 21)]
On post-SDT MRIs
Extent of targeted tumor area receiving FUS [Day 0]
Use of NaviFUS system to target a maximum of 50% of the tumor volume of one contiguous lesion
Ability to have participants undergo planned surgery without delay [within 3 weeks following SDT]
A delay is defined as more than 3 weeks after SDT

Secondary Outcome Measures

Response of target tissue following SDT on imaging [From day after SDT (day 1) up to 100 days after intervention is completed]
Via MRI w/ use of modified Response Assessment in Neuro-Oncology (RANO) criteria
Histologic tumor devitalization [Day 7-Day 21]
Evaluating cell fate and cell death via histologic samples after GBM resection

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 ≥ 6 cm3 and ≤ 20 cm3 of targeted treatment area
Tumor tissue to be treated is in a surgically accessible brain region for biopsy or resection
The brain tumor to be treated must be in the treatment envelope of the NaviFUS system (30 mm to 80 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):

Hematological

Absolute neutrophil count (ANC) ≥1000/mm3
Platelets ≥ 100,000/mm3
Hemoglobin ≥ 11 g/dL for women and ≥ 12 g/dL for men Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.
INR ≤ 1.4

Renal & Hepatic

Creatinine clearance CrCl ≥ 60 mL/min/1.73 m2 as estimated by the Cockcroft-Gault (C-G) equation. If estimated CrCl is abnormal, accurate measurement should be obtained by 24- hour CrCl.
Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 2.0x ULN is allowed).
AST and ALT ≤ 3 x ULN
Alkaline phosphatase ≤ 3 x ULN
GGT ≤ 3 x ULN
Estimated glomerular filtration rate ≥30mL/min/1.73m2

Exclusion Criteria:

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
Serious and inadequately controlled cardiac arrhythmia
Acute exacerbation of chronic obstructive pulmonary disease
Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
Treatment with another investigational drug within 30 days prior to registration or within 5 half-lives of the investigational product, whichever is longer
Brain edema and/or mass effect that causes midline shift of more than 15 mm
Evidence of recent (within 30 days prior to registration) intracranial hemorrhage
Calcifications or metallic implanted objects in the focused ultrasound sonication path
Scalp atrophy or scars at the expected location of transducer
Cerebral or systemic vasculopathy
Need for or currently on dialysis
Respiratory: chronic pulmonary disorders (e.g., severe emphysema, COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area).
Receipt of radiotherapy ≤21 days prior to registration
Receipt of any of the following ≤ 21 days prior to registration

chemotherapy
any investigational medications or investigational procedures

Prior treatment with sonodynamic therapy
Concurrent use of Optune device
Concurrent use of supplements or medications with substantial antioxidant effects (including sulfhydryl-containing medications such as captopril or supplements such as N-acetylcysteine, or high doses of vitamins with antioxidant activity such as C or E)
Known sensitivity to gadolinium