search
Back to results

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

Primary Purpose

BCLC Stage A Hepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
18F-Fluoromisonidazole
Biopsy
Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Positron Emission Tomography
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for BCLC Stage A Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Emory University Hospital/Winship Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (18F-fluoromisonidazole, PET, DCE MRI)

Arm Description

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.

Outcomes

Primary Outcome Measures

To investigate the variability of hypoxia in HCC at baseline as quantified by BOLD MRI
Threshold <1.0 R2 tumor to normal ratio (no unit) as a cutoff for hypoxia
To investigate the variability of hypoxia in HCC at baseline as quantified by immunohistochemistry
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).

Secondary Outcome Measures

Determine whether hypoxia is predictor of response in HCC treated with Y90 SIRT
Treatment Response Assessment using mRECIST
Treatment response
Assessed using modified Response Evaluation Criteria in Solid Tumors.

Full Information

First Posted
December 22, 2021
Last Updated
May 9, 2023
Sponsor
Emory University
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT05250895
Brief Title
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
Official Title
Molecular Imaging of the Hypoxic Tumor Microenvironment to Predict Response to Yttirum-90 Selective Internal Radiation Therapy in Hepatocellular Carcinoma- Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 28, 2022 (Actual)
Primary Completion Date
January 30, 2024 (Anticipated)
Study Completion Date
January 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
BCLC Stage A Hepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma, Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (18F-fluoromisonidazole, PET, DCE MRI)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
18F-Fluoromisonidazole
Other Intervention Name(s)
18F-MISO, 18F-Misonidazole, FMISO
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Procedure
Intervention Name(s)
Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Other Intervention Name(s)
DCE, DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI
Intervention Description
Undergo DCE MRI
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo PET
Primary Outcome Measure Information:
Title
To investigate the variability of hypoxia in HCC at baseline as quantified by BOLD MRI
Description
Threshold <1.0 R2 tumor to normal ratio (no unit) as a cutoff for hypoxia
Time Frame
From weeks 1-2 up to 1 year
Title
To investigate the variability of hypoxia in HCC at baseline as quantified by immunohistochemistry
Description
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).
Time Frame
From weeks 1-2 up to 1 year
Secondary Outcome Measure Information:
Title
Determine whether hypoxia is predictor of response in HCC treated with Y90 SIRT
Description
Treatment Response Assessment using mRECIST
Time Frame
From week 0 up to 1 year
Title
Treatment response
Description
Assessed using modified Response Evaluation Criteria in Solid Tumors.
Time Frame
From week 0 Up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nima Kokabi, MD, FRCPC
Phone
(404) 778-4747
Email
nkokabi@emory.edu
First Name & Middle Initial & Last Name or Official Title & Degree
David Schuster, MD
Phone
404-712-4859
Email
dschust@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nima Kokabi, MD, FRCPC
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Rivas
Phone
404-712-7962
Email
mrivas2@emory.edu
First Name & Middle Initial & Last Name & Degree
Nima Kokabi, MD, FRCPC

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs