Sonodynamic Therapy in Patients With Recurrent GBM

NCT ID: NCT06039709

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2026-06-30

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.

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.

Conditions

Recurrent Glioblastoma; Glioblastoma Multiforme; GBM

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sonodynamic Therapy (5-ALA + LIFU)

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

Group Type: EXPERIMENTAL

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

Intervention Type: COMBINATION_PRODUCT

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

Interventions

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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 ≥ 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

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shayan Moosa, MD

OTHER

Sponsor Role: lead

Responsible Party

Shayan Moosa, MD

Assistant Professor of Neurosurgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shayan Moosa, MD

Role: PRINCIPAL_INVESTIGATOR

UVA

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zachary Sturgill

Role: CONTACT

Phone: 434-243-9986

Email: FFM7RC@uvahealth.org

Judith Beenhakker, M.S.

Role: CONTACT

Phone: 434-982-1856

Email: jgb3p@uvahealth.org

Facility Contacts

Zachary Sturgill

Role: primary

Judith Beenhakker, MS

Role: backup

Other Identifiers

HSR230064

Identifier Type: -

Identifier Source: org_study_id