Sonodynamic Therapy in Patients With Recurrent GBM

Glioblastoma Multiforme Clinical Trial

— GBM 001  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06039709
• Other study ID #: HSR230064
• Status: Recruiting
• Phase: Phase 1
• Start date: January 31, 2024
• Est. completion date: June 2026

Study information

• Verified date: February 2024
• Source: University of Virginia
• Contact: Zachary Sturgill
• Phone: 434-243-9986
• Email: FFM7RC[@]uvahealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. 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 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

2. Men or women between the ages of 18-80 years of age at the time of consent

3. No contraindication to repeat brain surgery

4. Karnofsky Performance Score of 70-100

5. Able to undergo an MRI with contrast

6. Able to swallow oral medications

7. Willingness and ability to comply with scheduled visits, treatment plans, lifestyle considerations, laboratory tests, and other procedures.

8. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).

9. 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.

10. 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:

1. Known sensitivity or allergy to 5-ALA

2. Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)

3. Diagnosis of porphyria

4. Hypersensitivity against porphyrins

5. Pregnancy

6. Significant cardiac disease or coagulopathy

7. Herniation / intractable seizure / other clinical indications requiring urgent resection

8. 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)

9. Have had a recent (=3 months prior to registration) transient ischemic attack or stroke

10. Significant vascular disease (e.g. aortic aneurysm)

11. Evidence of bleeding diathesis or coagulopathy

12. Need for systemic anticoagulation which cannot be held for 7 days prior to SDT

13. Unstable angina and/or congestive heart failure (NYH Class III or Class IV; see section 13.2) within 6 months prior to registration

14. Severe hypertension (systolic = 180 mm Hg; diastolic = 120 mm Hg) despite anti-hypertensive medications

15. Transmural myocardial infarction within 6 months prior to registration

16. Serious and inadequately controlled cardiac arrhythmia

17. Acute exacerbation of chronic obstructive pulmonary disease

18. Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

19. Treatment with another investigational drug or investigational procedure within 30 days prior to registration or within 5 half-lives of the investigational product, whichever is longer

20. Brain edema and/or mass effect that causes midline shift of more than 15 mm

21. Evidence of recent (within 30 days prior to registration) intracranial hemorrhage

22. Calcifications or metallic implanted objects in the focused ultrasound sonication path

23. Scalp atrophy or scars at the expected location of transducer

24. Cerebral or systemic vasculopathy

25. Need for or currently on dialysis

26. Respiratory: chronic pulmonary disorders (e.g., severe emphysema, COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area).

27. Receipt of radiotherapy =21 days prior to registration

28. Receipt of chemotherapy = 21 days prior to registration

29. Prior treatment with sonodynamic therapy

30. Concurrent use of Optune device

31. 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)

32. Known sensitivity to gadolinium

Related Conditions & MeSH terms

• GBM
• Glioblastoma
• Glioblastoma Multiforme
• Recurrence
• Recurrent Glioblastoma

Intervention

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.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Shayan Moosa, MD

Country where clinical trial is conducted

United States, 

Outcome

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