Utilize Imaging to Assess Changes in Hepatocellular Carcinoma Perfusion as Potentiated by Intra-Arterial Nitroglycerin

Utilizing Parenchymal Blood Volume Imaging to Assess Changes in Hepatocellular Carcinoma Perfusion as Potentiated by Intra-Arterial Nitroglycerin

This is a single-arm, open-label, single-center, first-in-human feasibility study evaluating parenchymal blood volume (PBV) imaging as a tool to dynamically assess perfusional changes in hepatocellular carcinoma (HCC) potentiated by intra-arterial administration of nitroglycerin.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC); Liver Cancer, Adult
• Intervention / Treatment: Procedure: Parenchymal Blood Volume (PBV) Imaging; Drug: Nitroglycerin; Other: Medical Record Review

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate in vivo, parenchymal blood volume imaging's ability to dynamically assess blood flow to hepatocellular carcinoma.

SECONDARY OBJECTIVES:

1. Quantitative measurement of tumor perfusion after intra-arterial injection of nitroglycerin using parenchymal blood volume imaging.

OUTLINE:

Participants will undergo parenchymal blood volume (PBV) imaging before and after intra-arterial nitroglycerin injection during their standard transarterial chemoembolization (TACE) treatment. Participants will be followed on days 3, 7, 30, and 90 after the procedure.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Diana Flores; Phone Number: 415-514-6221; Email: diana.flores@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Contact: Diana Flores; Phone Number: 415-514-6221; Email: diana.flores@ucsf.edu
      • Principal Investigator: Christopher Brunson, MD
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital (ZSFG)
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Contact: Diana Flores; Phone Number: 415-514-6221; Email: diana.flores@ucsf.edu
      • Principal Investigator: Christopher Brunson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must have radiographically documented, previously untreated LIRADS V liver lesions or biopsy-confirmed hepatocellular carcinoma (HCC), as determined by the ZSFG Liver Tumor Board.
2. Lesions must be determined to be suitable for conventional trans-arterial chemoembolization (cTACE) based on multidisciplinary tumor board review.
3. No prior locoregional therapy (e.g., TACE, Y-90) to the index lesion(s).
4. Age ≥18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky >70%)

6. Demonstrates adequate organ function as defined below:

   1. Absolute neutrophil count >=1,500/microliter (mcL).
   2. Platelets ≥100,000/microliter (mcL).
   3. Total bilirubin ≤ 3.0 milligrams per deciliter (mg/dL), unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
   4. Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) ≤3 X institutional upper limit of normal.
   5. Alanine aminotransferase (ALT) / serum glutamic-oxaloacetic transaminase (SGPT) ≤3 X institutional upper limit of normal
   6. Creatinine ≤ 1.5 x within institutional upper limit of normal or
   7. Creatinine clearance Glomerular filtration rate (GFR) >= 60 milliliters per minute (mL/min)/1.73 m2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 milliliters per minute (mL/min)/1.73 m2.
7. Liver function: Child-Pugh score must be no higher than B5.
8. Ability to understand and the willingness to sign a written informed consent document.
9. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
10. The female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception during the study and for 30 days after study intervention.

Exclusion Criteria:

1. Multifocal disease (i.e., presence of more than one HCC lesion).
2. Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of LHRH analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.
3. Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).
4. Is currently receiving any other therapeutic/investigational agents.
5. Has participated in a study of an investigational product and received study treatment or used an investigational device within 3 weeks of the first use of an investigational product.
6. Co-morbid disease or concurrent illness (e.g., cardiovascular disease, portal vein thrombosis).
7. Hypersensitivity to nitroglycerine or any of its excipients.

8. Concomitant medications (contraindicated):

   1. Concurrent use of prescription phosphodiesterase inhibitors (e.g., sildenafil)
   2. Concurrent use of nitrate-containing medications.
   3. Concurrent use of vasoactive chemotherapeutic agents, such as bevacizumab (Avastin).

9. Recent anti-cancer therapies:

   1. Systemic anticancer therapies within 3 weeks of the procedure.
   2. Radiation therapy within 2 weeks.
   3. Antibody-based therapy within 4 weeks.
   4. Use of investigational agents or devices within 3 weeks of the index procedure.
10. Unresolved toxicities from prior cancer therapy, unless ≤ Grade 1 (excluding alopecia).
11. Currently receiving any other therapeutic or investigational agents during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nitroglycerin Injection; Participants with confirmed hepatocellular carcinoma (HCC) will undergo parenchymal blood volume (PBV) imaging before and after intra-arterial nitroglycerin injection during standard transarterial chemoembolization (TACE) treatment. Nitroglycerin doses ranging from 200-300 micrograms will be administered based on patient body mass index (BMI) and interventional radiology standards. Participants will be followed either in person or via telehealth on days 3, 7, 30, and 90 for safety and post-procedural assessment, until withdrawal from the study or death, whichever occurs first.

Procedure: Parenchymal Blood Volume (PBV) Imaging; Undergo imaging; Other Names: PBV; Drug: Nitroglycerin; Given Intra-Arterially; Other: Medical Record Review; Data will be collected from the participant medical records.; Other Names: Medical Chart Review

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with >= 30% increase in Tumoral Blood Volume	Proportion of participants who demonstrate an increase in tumoral blood volume of at least 30% following intra-arterial nitroglycerin administration compared with pre-nitroglycerin baseline along with Bonferroni-corrected confidence intervals will be reported.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with >= 50% increase in Tumor-to-Normal Ratio	Proportion of participants demonstrating at least a 50% increase in the tumor-to-normal ratio on parenchymal blood volume imaging following intra-arterial nitroglycerin administration compared with pre-nitroglycerin baseline along with Bonferroni-corrected confidence intervals will be reported.	Day 1

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Christopher Brunson, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: TACE; Transarterial Chemoembolization; Tumor Perfusion; Parenchymal Blood Volume Imaging; Intra-Arterial Nitroglycerin
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Organic Chemicals; Physical Phenomena; Electromagnetic Phenomena; Magnetic Phenomena; Nitro Compounds; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Nitroglycerin; X-Rays
• Other Study ID Numbers: 26323; NCI-2026-04001 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes