Study of Sonodynamic Therapy in Participants With Recurrent High-Grade Glioma

• ClinicalTrials.gov Identifier: NCT04559685
• Recruitment Status: Recruiting
• First Posted: September 23, 2020
• Last Update Posted: March 22, 2021
• Sponsor: Nader Sanai
• Collaborators: Barrow Neurological Institute; Ivy Brain Tumor Center; SonALAsense; InSightec
• Information provided by (Responsible Party): Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix

Tracking Information

• First Submitted Date: September 11, 2020
• First Posted Date: September 23, 2020
• Last Update Posted Date: March 22, 2021
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2020)

Biological changes associated with the sonodynamic therapy [ Time Frame: Intraoperatively 2, 4, or 6 days post sonodynamic therapy ]

The percentage (%) of Cleaved Caspase-3, MIB-1 level, GammaH2Ax of the surgical tissue will be quantified and compared to intra-patient control specimens.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 16, 2020)

• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy [ Time Frame: Pre and 14 Days Post-operative scan ]
  Dynamic Contrast Enhanced (DCE)-MRI data to quantify permeability
• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy [ Time Frame: Pre and 14 Days Post-operative scan ]
  Dynamic Susceptibility Contrast (DSC)-MRI data to quantify perfusion
• Radiographic evidence of tumor physiological imaging changes associated with sonodynamic therapy [ Time Frame: Pre and 14 Days Post-operative scan ]
  Diffusion Weighted Imaging (DWI) data to evaluate cellularity
• To identify oxidative stress in tissue exposed to sonodynamic therapy in recurrent high-grade glioma patients. [ Time Frame: Intraoperatively 2, 4, or 6 days post sonodynamic therapy ]
  To quantify markers for oxidative stress (Protein oxidation (Protein Carbonyl Content), Lipid peroxidation (4-hydroxynonenal and MDA), DNA damage (8-hydroxyguanosine),General (GSH, GSSG, Cys, CySS) in the brain tumor tissue (2-, 4- and 6-days post SDT) (both in SDT and control fractions)
• Performance of MRgFUS [ Time Frame: Day 1 ]
  Percentage of SDT treatments in which the MRgFUS system works as planned
• Performance of MRgFUS [ Time Frame: Day 1 ]
  Percentage of treatments in which procedure deviations were noted
• Safety and Tolerability [ Time Frame: up to 30 days after the last study dose ]
  Number and incidence of drug-related toxicity
• Safety and Tolerability [ Time Frame: up to 30 days after the last study dose ]
  Adverse device effects

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Sonodynamic Therapy in Participants With Recurrent High-Grade Glioma
• Official Title: A Phase 0, First in Human, Open-label Study of Intravenous Aminolevulinic Acid HCl (ALA) and MR-Guided Focused Ultrasound Device (MRgFUS) in Participants With Recurrent High Grade Glioma (HGG)
• Brief Summary: A Phase 0 single center, first in human, open-label study of ascending energy doses of sonodynamic therapy (SDT) utilizing the MRgFUS combined with intravenous ALA to assess safety and efficacy in up to 30 participants with recurrent HGG. Eligible participants who are scheduled for resection will be administered intravenous (IV) aminolevulinic acid HCl (ALA) approximately six to seven (6-7) hours prior to receiving sonodynamic therapy (SDT).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: High Grade Glioma

Intervention

Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

SONALA-001(ALA) given 6-7 hours prior to receiving the MRgFUS.

Study Arms

• Experimental: Arm A Dose-escalation
  In Arm A, the dose-escalation cohort, there will be 3 cohorts of ascending MRgFUS power/energy dose combinations with a fixed SONALA-001 dose and fixed surgical time. Arm A will determine the power/energy dose combination for Arm B.
  Intervention: Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)
• Experimental: Arm B Time-escalation
  In Arm B, the time-escalation cohort, the SONALA-001 and power/energy dose combination will be fixed. Participants will be enrolled into two time cohorts (2 days and 6 days post-SDT).
  Intervention: Combination Product: SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 16, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2022
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as participants who have progressed on or following standard (Stupp regimen) therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy.
2. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI with positive perfusion.
3. Have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with a volume of at least 6 cm3 and ≤ 20cm3 of targeted treatment area.
4. Age ≥18 at time of consent.
5. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982).
6. Ability to swallow oral medications.

7. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility)

   Adequate bone marrow function:

   • absolute neutrophil count ≥1,000/mcL
   • Platelets (at time of surgery) ≥100,000/mcL
   • hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.

   Adequate hepatic and renal function:

   • total bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
   • AST(SGOT) ≤3 X institutional ULN
   • ALT(SGPT) ≤3 X institutional ULN
   • GGT ≤3 X institutional ULN
   • Serum creatinine ≤1.5 X institutional ULN
8. Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant has had a hysterectomy.
9. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the end of treatment administration.
10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 1 month after the end of treatment administration. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid.
11. Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy dose and Day 1 (provided the patient did not receive radiotherapy).
12. Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and Day 1.
13. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
14. Has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
15. Willingness and ability to comply with scheduled visits, treatment plans, Lifestyle Considerations, laboratory tests and other procedures.

Exclusion Criteria:

1. 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]. Screening is not required for enrollment.
2. Have had a recent (≤3 months prior to first dose of study drug) transient ischemic attack or stroke.
3. Significant vascular disease (e.g. aortic aneurysm)
4. Evidence of bleeding diathesis or coagulopathy
5. Diagnosis of porphyria
6. Unstable angina and/or congestive heart failure within the last 6 months
7. Transmural myocardial infarction within the last 6 months
8. Serious and inadequately controlled cardiac arrhythmia
9. Acute exacerbation of chronic obstructive pulmonary disease
10. Inability to undergo MRI (e.g., presence of a pacemaker)
11. Pregnancy or breastfeeding
12. Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
13. Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
14. Hypersensitivity against porphyrins
15. Treatment with another investigational drug within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
16. Has an Overall Skull Density Ratio of 0.45 (±0.05) or less as calculated from the screening CT.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Phase 0 Navigator; 602-406-8605; research@ivybraintumorcenter.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04559685
• Other Study ID Numbers: 2020-11; 21-500-032-34-38 ( Other Identifier: St. Joseph's Hospital and Medical Center )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix
• Study Sponsor: Nader Sanai

Collaborators

• Barrow Neurological Institute
• Ivy Brain Tumor Center
• SonALAsense
• InSightec

Investigators

• Principal Investigator: Nader Sanai, MD; St. Joseph's Hospital and Medical Center, Phoenix

• PRS Account: St. Joseph's Hospital and Medical Center, Phoenix
• Verification Date: March 2021