Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization
Condition: Liver Cancer; Liver Neoplasm; Hepatocellular Carcinoma; HCC
MeSH terms: Liver Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Treatment for liver cancer can include surgery, transplant, and chemotherapy. It can also
      include other minimally invasive tumor treatments such as transarterial chemoembolization
      (TACE). TACE treatment for liver cancer helps control the cancer but is not considered a
      cure. Researchers want to learn more about the effects of TACE on liver tumors and
      surrounding tissue. To do this, they will use a positive emission test (PET) and a
      radioactive tracer called [18F] FMISO.

      Objectives:

      - To see if [18F] FMISO is useful for evaluating what happens to liver tumors and surrounding
      tissue after TACE.

      Eligibility:

      - People age 18 and older with liver cancer who have been approved to have TACE.

      Design:

        -  Participants will meet with a study researcher to see if they can take part in the
           study.

        -  Participants will have TACE under a separate NCI protocol or at a hospital other than
           the NIH Clinical Center.

        -  Before and after TACE, participants will have a CT and MRI of the abdomen. For these
           scans, they will lie in a machine that takes pictures of their body. They will also have
           blood tests and a physical exam.

        -  The [18F] FMISO imaging study will be performed at NIH only.

        -  Participants will have an intravenous catheter placed in their arm (if they do not have
           one). The [18F] FMISO tracer will be injected.

        -  Participants will have PET-CT scans. Each scan will take about 30 minutes.

        -  Some participants will also have [18F] FMISO and PET-CT scans before TACE.

        -  As part of standard care for TACE, participants will have CT and MRI scans at regular
           intervals. This will evaluate tumor response.
    

Detailed description: 
      Background

        -  TACE is the standard therapy for inoperable primary liver cancers or tumor control prior
           to transplantation. The mechanisms for TACE s failure remains poorly understood.

        -  Although acute hypoxia and significant tumor necrosis occurs following TACE, the tumor
           adaptive response and localization for such have not been well characterized.

        -  Imaging tools using a hypoxia-specific tracer [(18)F] FMISO may help identify the
           pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated tumor
           progression.

        -  The primary hypothesis of this study states that tumor progression post-TACE arises from
           changes in tumor phenotype induced by treatment-related hypoxia superimposed on the
           dynamic process of underlying tumor hypoxia.

      Objectives

      -To determine the feasibility of hypoxic tumor identification despite relatively high liver
      background signal, and describe patterns of tumor hypoxia in the immediate post-TACE
      treatment period using PET imaging [(18)F] MISO uptake registered with cross-sectional
      imaging.

      Eligibility

        -  Patients greater than or equal to 18 years with inoperable primary hepatic malignancy or
           hepatic-dominant metastatic-disease and be otherwise eligible to receive TACE treatment.
           Patients with hepatocellular carcinoma should have intermediate stage disease according
           to the BCLC staging system (Stage A4 or B).

        -  Patients must not have had chemotherapy- or radiation therapy to liver for at least 2
           weeks prior to starting study treatments.

        -  Patients must not have an acute, critical illness.

        -  Patients must not be pregnant

        -  Able to understand and be willing to sign a written informed consent

      Design

        -  Fifteen patients with primary or metastatic liver malignancy will be enrolled into this
           pilot, non-randomized, open study of the feasibility of using (18)F-fluoromisonidazole
           PET scanning to determine hypoxic tumor identification and localization, and to identify
           the pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated
           tumor progression.

        -  Twenty-four to seventy-two hours after standard of care TACE, patients will undergo

      PET scanning using 0.1mCi/kg (maximum 10mCi) of (18)F-fluoromisonidazole [(18)F] MISO).
    

Intervention name(s): [18F] FMISO
Intervention type(s): Drug
Intervention description(s): [18F] Fluromisonidazole, 1 h-(3-[18F]-fluro-2hydroxyl-propy10-2-nitro-imidazaole is an investigational positron emission tomography (PET) radiopharmaceutical for injection and used to visualize hypoxia imaging agent. Each patient will receive up to 10 mCi of [18F] FMISO PET imaging post TACE procedure.
Other intervention name(s): FMISO
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Cross-Sectional Imaging; Chemoembolization; Radiation Therapy; Tumor Hypoxia; PET Imaging