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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05250895
• Other study ID #: STUDY00002804
• Secondary ID: NCI-2021-09943ST
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 28, 2022
• Est. completion date: January 30, 2026

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: Nima Kokabi, MD, FRCPC
• Phone: (404) 778-4747
• Email: nkokabi[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 30, 2026
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• 18F-Fluoromisonidazole
Given IV

Procedure:
• Biopsy
Undergo biopsy
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo DCE MRI
• Positron Emission Tomography
Undergo PET

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	From weeks 1-2 up to 1 year
Primary	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).	From weeks 1-2 up to 1 year
Secondary	Determine whether hypoxia is predictor of response in HCC treated with Y90 SIRT	Treatment Response Assessment using mRECIST	From week 0 up to 1 year
Secondary	Treatment response	Assessed using modified Response Evaluation Criteria in Solid Tumors.	From week 0 Up to 1 year