Adjuvant Temozolomide ± 5-Aminolevulinic Acid + Low Intensity Diffuse Ultrasound Sonodynamic Therapy System for Newly Diagnosed Glioblastoma

NCT07225621 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CV01-201
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this research is to test an investigational device using ultrasound along with an investigational drug to see if it is useful in treating glioblastoma following standard of care therapy surgery and chemoradiation. This study is evaluating an experimental treatment for glioblastoma that uses an investigational drug (5-ALA) combined with a non-invasive ultrasound device (LIDU) to target tumor cells. Patients meeting the entry requirements to be in the study, will be equally randomly assigned to receive the study device plus the active study drug plus active ultrasound, or to a "sham" procedure where the ultrasound is not being activated and the study drug is a placebo (looks the same but does not contain active drug). Neither the patient or the investigator will know who is in the active group or not. Both groups will continue to receive the standard therapy of oral Temozolomide.

Conditions

Glioblastoma; GBM

Outcome Measures

Primary Outcomes (1)

• Evaluate and compare progression-free survival of patients by treatment arm

  Up to 24 months

Secondary Outcomes (4)

• Evaluate and compare overall survival of patients by treatment arm

  Up to 24 months

• Evaluate and compare survival at specific time points by treatment arm

  12, 18 and 24 months

• Evaluate the number of participants with treatment-related adverse events as assessed by CTCAE by treatment arm

  Up to 24 months

• Evaluate time to next treatment for 5-ALA + LIDU SDT System

  Up to 24 months

Other Outcomes (2)

• Identify and evaluate prognostic and predictive factors (e.g. MGMT, extent of resection) for PFS

  Up to 24 months

• Identify and evaluate prognostic and predictive factors (e.g. MGMT, extent of resection) for OS

  Up to 24 months

Study Arms (2)

Arm A: (experimental arm)

EXPERIMENTAL

* 5-ALA HCl (5-amino-levulenic acid) for oral solution (20 mg/kg) p.o. 6-8 hours prior to LIDU SDT * LIDU SDT System (low intensity diffuse ultrasound sonodynamic therapy), for 40 minutes followed by standard of care TMZ * SOC TMZ to be started Day 2 (+/-1 day) per the approved PI

Combination Product: 5-ALA HCl + LIDU SDT

Arm B: (placebo arm)

PLACEBO COMPARATOR

* Placebo oral solution (matched to 20 mg/kg) p.o. 6-8 hours prior to Sham SDT * Sham SDT for 40 mimnutes followed by standard of care TMZ * SOC TMZ to be started Day 2 (+/-1 day) per the approved PI

Combination Product: Placebo + Sham SDT

Interventions

5-ALA HCl + LIDU SDT COMBINATION_PRODUCT

standard of care temozolomide + sonosenitizer + sonodynamic therapy

Arm A: (experimental arm)

Placebo + Sham SDT COMBINATION_PRODUCT

standard of care temozolomide + placebo + sham sonodynamic therapy

Arm B: (placebo arm)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must provide informed consent, stating understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements
• ≥ 18 and ≤ 80 years of age
• WHO performance status of ≤ 2 at screening
• Newly diagnosed Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.
• GBM patients that have an absence of disease progression post craniotomy and TMZ/RT. Note: patients must have undergone prior tumor resection to the extent safely feasible (biopsy only are not eligible).
• Completion of chemoradiation consisting of radiotherapy (30 x 20 Gy, or equivalent regimen, eg 33 x 18 Gy), with ≥ 90% of the planned radiation therapy dose delivered and concomitant TMZ chemotherapy (75 mg/m2), \>66% of the planned doses administered.
• Any toxicity attributable to recently completed chemoradiation must be resolved to the patient's baseline level or ≤ Grade 2 (except alopecia or lymphopenia).
• Adequate bone marrow and organ function, defined by the following laboratory values: A. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 B. Platelet count ≥ 50,000 cells/mm3 C. Hemoglobin (Hgb) ≥ 8 g/dl D. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) E. Total bilirubin ≤ 3 x ULN (unless gilbert's syndrome, then patients may be eligible if total serum bilirubin is ≤ 5.0 x ULN or direct bilirubin is ≤ 3 x ULN) F. Creatinine clearance (CrCl) as estimated by Cockcroft-Gault equation of ≥ 50 ml/min
• Adequate coagulation function defined as PT (prothrombin time)/PTT (partial thromboplastin time) defined as either results within normal institutional values or not considered clinically significant \<1.5 x ULN.
• Non-pregnant, non-lactating females who are postmenopausal, surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation or hysterectomy), or who agree to use effective contraceptive methods as defined by the protocol during the study and for 30 days after the last investigational treatment, see Appendix 1. Postmenopausal is defined as at least 12 months natural spontaneous amenorrhea and a serum follicle stimulating hormone (FSH) concentration ≥ 40 IU/L, or at least 6 weeks following surgical menopause (bilateral oophorectomy). See Appendix 1, females on HRT and whose menopausal status is in doubt will be required to use one of the non-estrogen hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.
• Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days prior to first 5-ALA administration
• Male patients must be surgically sterile (i.e., 3 months post- vasectomy) or willing to use a highly effective double-barrier contraception method (e.g., male condom with diaphragm or male condom with cervical cap) for the duration of the study and for at least 30 days following SDT treatment. Male patients must not donate sperm from the time of study drug dosing until 30 days following SDT treatment.
• No anti-cancer treatment during adjuvant setting after completion of radiation therapy with anything other than temozolomide on Day 2 (+/-1 day) for 5 days per the approved Package Insert (PI).

You may not qualify if:

• Any component of the tumor in the infratentorial location (cerebellar or brainstem tumors are excluded)
• Bihemispheric disease or tumors that involve the bilateral corpus callosum, or disease burden involving the brain stem or cerebellum based on MRI post-gadolinium enhancement,
• Multi- centric disease (enhancing or non-enhancing) or multi-focal disease (defined as 2 separate areas of contrast enhancement measuring at least 1 cm that are not contiguous and cannot be encompassed in sonication field on either fluid-attenuated inversion recovery (FLAIR) or T2 hyperintensity.
• Leptomeningeal disease
• \. A diagnosis of glioscarcoma by histopathology Intent to undergo treatment with the tumor treating fields (TTF) at any time during the study, use prior to screening is permitted.

Sponsors & Collaborators

• Alpheus Medical, Inc.: lead

Study Sites (8)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Albany Medical Center

Albany, New York, 12208, United States

RECRUITING

Dent Neurologic Institute

Buffalo, New York, 14226, United States

RECRUITING

Northwell Health

Long Island City, New York, 11030, United States

RECRUITING

New York Langone

New York, New York, 10016, United States

NOT YET RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Ann-Marie VP, Clinical Operations

CONTACT

4842521960; AMHulstine@alpheusmedical.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2025
• First Posted: November 6, 2025
• Study Start: January 28, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

US (8)