Study of Ferumoxytol Enhanced MRI for Detecting Lymph Node Metastases in Prostate, Bladder, and Kidney Cancers
Condition: Prostate Cancer; Bladder Cancer; Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Lymphatic Metastasis
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      People with prostate, bladder, or kidney cancer often have their cancer spread (metastasize)
      to lymph nodes. It is important for your doctor to know if this has occurred but currently it
      can be hard to determine if this has occurred on standard imaging studies like computed
      tomography (CT) or magnetic resonance imaging (MRI). This study uses an agent called
      Ferumoxytol to identify lymph nodes that might be involved by cancer.

      Objective:

      - To see how well Ferumoxytol can detect lymph node metastases in patients with prostate,
      bladder, or kidney cancer.

      Eligibility:

      -Adults over age 18 with prostate, bladder, or kidney cancer with lymph node involvement.

      Design:

        -  Participants will be screened with a medical history.

        -  Participants will have blood drawn and a physical exam. Their vital signs will be
           measured. They will answer questions about their health and current medications.

        -  Participants should not have a history of iron overload or have an allergy to
           Ferumoxytol.

        -  Participants will have a magnetic resonance imaging (MRI) scan. The scanner is a metal
           cylinder with a strong magnetic field. Participants will lie on a table that slides in
           and out of the scanner. They will have a standard sensor, known as a coil, wrapped
           around their abdomen to improve the scan. This is like a small blanket with wiring
           inside. Participants will need to lie still on the scanning table for about 1 hour.

        -  Participants will have an ultrasound. This uses harmless sound waves to provide pictures
           of organs or tissues inside the body.

        -  Participants will receive an injection of Ferumoxytol through an intravenous line. A
           very thin plastic tube will be inserted into a vein in order to inject the agent.

        -  Participants will have another MRI and ultrasound 24 and 48 hours after injection.

        -  The study will follow participants medical course for at least 1 year.
    

Detailed description: 
      Background:

        -  Conventional imaging modalities (e.g. computed tomography [CT] and magnetic resonance
           imaging [MRI]) are currently used for the detection of lymph node metastases in many
           cancer types, including prostate, bladder and kidney cancers, however diagnosis is based
           on node enlargement which is neither sensitive nor specific (i.e. small nodes harbor
           metastases, large nodes can be hyperplastic).

        -  As a consequence, the standard of care is to remove numerous lymph nodes during surgery
           or to biopsy enlarged nodes to ascertain lymph node status.

        -  In 2003 Dextran coated ultra small superparamagnetic iron oxide particles (USPIO), also
           known as Ferumoxtran-10 (Combidex, AMAG Pharmaceuticals, Inc. Lexington, Massachusetts
           (MA), United States (US)) was shown to localize lymph node metastases with much greater
           accuracy than unenhanced MRI. Although a large study in prostate cancer was successful,
           and Food and Drug Administration (FDA) Advisory Panel did not recommend approval and the
           company abandoned the agent.

        -  In 2009 Ferumoxytol (Feraheme AMAG Pharmaceuticals, Inc. Lexington, MA, United States
           (US)) a semi-synthetic carbohydrate coated, magnetic iron oxide preparation similar to
           ferumoxtran 10 was approved for iron replacement therapy. Like ferumoxtran 10, this
           compound is taken up by normal lymph nodes and excluded from malignant nodal tissue.

        -  Results of a recent National Cancer Institute (NCI) trial (11-C-0098) in 15 patients
           revealed that using the dose of 7.5 mg/kg Fe is safe and yields homogenous and accurate
           signal changes in benign lymph nodes in comparison with the 4 and 6 mg/kg Fe doses. This
           dose was further tested in 5 patient's with known or suspected nodal involvement from
           prostate cancer and in four of five patients positive lymph nodes had a lower signal
           drop than the benign nodes. The one case in which there was uptake by positive nodes may
           have been on a vascular basis. This pilot study stimulated interest in a larger study
           involving a variety of cancer types.

      Primary Objective:

      -To compare the difference in signal between metastatic and normal nodes in prostate, kidney
      and bladder cancer patients.

      Eligibility

        -  Subject must be greater than or equal to 18 years old.

        -  Eastern Cooperative Oncology Group Performance score of 0 to 2.

        -  There are 3 parallel arms in this study. All patients must have evidence of lymph node
           involvement (with a short axis diameter greater than or equal to 1.5 cm).

        -  In addition:

        -  Arm 1: Subject must have a documented diagnosis of prostate cancer.

        -  Arm 2: Subject must have a documented diagnosis of bladder cancer (transitional cell
           carcinoma).

        -  Arm 3: Subject must have a documented diagnosis of kidney cancer (all renal cell cancer
           types).

      Design:

        -  This is a single site 3-arm (arm 1=prostate cancer, arm 2=bladder cancer, arm 3=kidney
           cancer) study enrolling 50 evaluable patients (30 evaluable in each arm 1, 10 evaluable
           in arms 2 and 3) with documented prostate, bladder or kidney cancer with evidence of
           lymph node involvement [with a size of greater than or equal to 1.5 cm measured on
           conventional imaging (e.g. CT, MRI)].

        -  All subjects will undergo pre-infusion, 24, 48 hours post-Ferumoxytol infusion (dose of
           7.5mg/kg Fe) MRI consisting of T1 weighted (W), T2W and T2*W 3 Tesla MRI.

        -  Imaging will be correlated with histology of resected or biopsied lymph nodes when
           available. Occasionally, patients may not undergo biopsy or surgical excision of their
           lymph nodes. This may occur if their lymph nodes are overtly large and therefore highly
           likely to represent lymph node involvement. In such cases, patients will be evaluated
           with clinical follow up which typically occurs every three months in most NCI protocols.
           If the lesion demonstrates growth or regression based on Response Evaluation Criteria in
           Solid Tumors (RECIST) 1.1 criteria on these follow up studies' then the lesion will be
           considered positive for tumor. If it is stable for at least one year, then it will be
           considered non-malignant. The MR imaging analysis will be intra-patient.

        -  Patients will also undergo ultrasound examination of imageable lymph nodes (e.g.
           inguinal nodes) at pre-infusion and 24, 48 hours post-Ferumoxytol infusion time points.
           The signal changes at post-infusion ultrasound will be visually evaluated to determine
           if the uptake of ferumoxytol alters sonographic features.
    

Intervention name(s): Ferumoxytol; Magnetic Resonance Imaging (MRI)
Intervention type(s): Drug; Diagnostic Test
Intervention description(s): 7.5mg/kg intravenous (IV) infusion; 3 MRIs: pre-infusion, 24 and 48 hours post-infusion
Other intervention name(s): Feraheme
Intervention MeSH terms: Ferrosoferric Oxide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Lymph Node; Biopsy; Metastatic Nodes; Imaging Agent