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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Other: 18F-Fluoromisonidazole
* Procedure: Biopsy
* Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (18F-fluoromisonidazole, PET, DCE MRI)<br>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. | Other: 18F-Fluoromisonidazole<br>* Given IV<br>* Other names: FMISO;Procedure: Biopsy<br>* Undergo biopsy<br>* Other names: Bx;Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DCE MRI<br>* Other names: DYNAMIC CONTRAST ENHANCED MRI;Procedure: Positron Emission Tomography<br>* Undergo PET<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Treatment response | Assessed using modified Response Evaluation Criteria in Solid Tumors. | From week 0 Up to 1 year |