Sonodynamic Therapy in Patients With Recurrent GBM

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Incidence of adverse events [Time frame: From informed consent through 30 days after study intervention is complete]
• Severity of adverse events [Time frame: From informed consent through 30 days after study intervention is complete]
• Incidence of intracranial hemorrhage and/or worsening of edema [Time frame: From day after SDT (day 1) up to the time of surgery (day 7-day 21)]
• Extent of targeted tumor area receiving FUS [Time frame: Day 0]
• Ability to have participants undergo planned surgery without delay [Time frame: within 3 weeks following SDT]

Secondary outcome measures (2)

• Response of target tissue following SDT on imaging [Time frame: From day after SDT (day 1) up to 100 days after intervention is completed]
• Histologic tumor devitalization [Time frame: Day 7-Day 21]

Eligibility criteria

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 ≥ 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):

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

• 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 or investigational procedure 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 chemotherapy ≤ 21 days prior to registration
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Virginia — Charlottesville

Identifiers

NCT: NCT06039709 · HSR230064

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗