BOLD MRI and FMISO PET for the Assessment of Hypoxic Tumor Microenvironment in Patients with Oligometastatic Liver Cancer Undergoing Yttirum-90 Selective Internal Radiation Therapy

March 11, 2025 updated by: David Brandon, Emory University

Molecular Imaging of the Hypoxic Tumor Microenvironment to Predict Response to Yttirum-90 Selective Internal Radiation Therapy in Hepatocellular Carcinoma- Pilot Study

This early phase I trial evaluates the use of hypoxia (lack of oxygen) as a measure in determining the outcome of Y90 selective internal radiation therapy in patients with liver cancer that has spread to a limited number of sites (oligometastatic). Radioembolization with Y90 is a minimally invasive procedure that combines embolization and radiation therapy to treat metastatic liver cancer. Tiny beads filled with radioactive isotope Y-90 are placed inside the blood vessel that provide blood supply to the tumor. This will block the blood flow to the tumor cells while providing a high radiation dose without harming healthy normal tissue.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To investigate the variability of hypoxia in hepatocellular carcinoma (HCC) as quantified by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and dynamic 18F-Fluoromisonidazole (FMISO) positron emission tomography (PET).

SECONDARY OBJECTIVES:

I. Investigate whether hypoxia, as quantified by BOLD MRI, dynamic FMISO PET, HIF-1alpha and VEGF expression, predicts HCC response to yttrium-90 (Y90) selective internal radiation therapy (SIRT).

II. Assess whether hypoxia quantification by BOLD MRI, dynamic FMISO, HIF-1alpha or VEGF expression individually or in combination more accurately predict the degree of HCC tumor response to Y90 SIRT.

III. Compare the tumor dose response threshold between hypoxic and non-hypoxic HCCs treated with Y90 SIRT.

OUTLINE:

Patients receive 18F-fluoromisonidazole intravenously (IV) and undergo PET and dynamic contrast enhanced (DCE) MRI within 30 days before beginning Y90 SIRT. Patients undergo Y90 SIRT per standard of care.

After completion of study intervention, patients are followed up at 90 days, and then every 12 weeks thereafter.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age >= 18 years
  • Established HCC diagnosis, unilobar or bilobar disease
  • At least 1 tumor >= 3 cm
  • Oligometastatic disease
  • Barcelona Clinic Liver Cancer (BCLC) stage A, B or C
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy > 12 weeks as determined by the Investigator
  • The effects of Y90 Radioembolization on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
  • FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months

Exclusion Criteria:

  • Patients who are definite transplant candidates
  • Concurrent second malignancy outside of the liver
  • Infiltrative liver tumor
  • Previous liver-directed therapy to targeted tumors
  • BCLC stage D
  • Bilirubin > 2 mg/dL for lobar treatment and bilirubin > 3 mg/dL for segmental or bi-segmental Y90-SIRT
  • Albumin < 3 g/dL
  • Projected lung dose of > 30 Gy in a single session to the liver after prospective treatment planning
  • Body mass index (BMI) > 40

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diagnostic (18F-fluoromisonidazole, PET, DCE MRI)
Patients receive 18F-fluoromisonidazole IV and undergo PET and DCE MRI within 30 days before beginning Y90 SIRT. Patients undergo Y90 SIRT per standard of care.
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
Procedure: Biopsy
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo DCE MRI
Other Names:
  • DCE-MRI
  • DCE MRI
  • DYNAMIC CONTRAST ENHANCED MRI
  • DCE
Other: 18F-Fluoromisonidazole
Given IV
Other Names:
  • FMISO
  • 18F-MISO
  • 18F-Misonidazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To investigate the variability of hypoxia in HCC at baseline as quantified by BOLD MRI
Time Frame: From weeks 1-2 up to 1 year
Threshold <1.0 R2 tumor to normal ratio (no unit) as a cutoff for hypoxia
From weeks 1-2 up to 1 year
To investigate the variability of hypoxia in HCC at baseline as quantified by immunohistochemistry
Time Frame: From weeks 1-2 up to 1 year
The staining intensity will be measured and scored with four scales: no staining=0, weak staining=1, moderate staining=2, and strong staining=3. The final staining score will be obtained by stained stumor area% x positive tumor cells % x staining intensity. The tumors will be then categorized as hypoxic (scores 8 to 16) vs. non-hypoxic (scores 0 to 7) (no units).
From weeks 1-2 up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine whether hypoxia is predictor of response in HCC treated with Y90 SIRT
Time Frame: From week 0 up to 1 year
Treatment Response Assessment using mRECIST
From week 0 up to 1 year
Treatment response
Time Frame: From week 0 Up to 1 year
Assessed using modified Response Evaluation Criteria in Solid Tumors.
From week 0 Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Nima Kokabi, MD, FRCPC, Emory University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2022

Primary Completion (Actual)

February 26, 2025

Study Completion (Actual)

February 26, 2025

Study Registration Dates

First Submitted

December 22, 2021

First Submitted That Met QC Criteria

February 21, 2022

First Posted (Actual)

February 22, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 11, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00002804
  • P30CA138292 (U.S. NIH Grant/Contract)
  • NCI-2021-09943 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RAD5342-21 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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