Ferumoxytol Enhanced MRI for the Detection of Lymph Node Involvement in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Ferumoxytol is an approved iron replacement therapy agent that has some potential for use
      as a contrast agent in imaging studies of the lymph system, especially involving lymph nodes
      that have been affected by cancer. Ferumoxytol is taken up by normal lymph nodes, but
      excluded from cancerous lymph node tissue. Because Ferumoxytol has not yet been approved for
      use as an imaging agent, researchers are interested in testing its effectiveness as a
      contrast agent for studies of normal lymph tissue and cancer tissue in lymph nodes of
      individuals with prostate cancer.

      Objectives:

      - To evaluate the safety and effectiveness of Ferumoxytol as a contrast agent in individuals
      who are scheduled to have prostate removal surgery to treat prostate cancer.

      Eligibility:

      - Men at least 18 years of age who have been diagnosed with prostate cancer and are scheduled
      to have surgery to remove the prostate and surrounding lymph nodes.

      Design:

        -  Participants will be screened with a full medical history and physical examination,
           blood and urine tests, and tumor imaging studies.

        -  Participants will have a magnetic resonance imaging (MRI) scan to provide baseline
           images for the study.

        -  Participants will receive an injection of Ferumoxytol and will return for another MRI
           scan on the following day (around 24 hours later).

        -  Some participants may have a third MRI scan 48 hours after the initial injection of
           Ferumoxytol. This third MRI scan is optional and not required by the study.

        -  Although the scanning and followup portion of the study will last only a few days,
           participants will be considered to be enrolled on the study until after the prostate
           removal surgery.
    

Detailed description: 
      Background:

        -  Prostate cancer is the most common non-cutaneous malignancy among men in Western world.
           Accurate lymph node staging is important in treatment planning for prostate cancer.

        -  Conventional imaging modalities (e.g. computed tomography [CT] and magnetic resonance
           imaging [MRI]) are used for the evaluation of lymph node involvement in many cancer
           types, including prostate cancer, however diagnosis is based on node enlargement which
           is neither sensitive nor specific in prostate cancer.

        -  As a consequence, the standard of care is to remove numerous lymph nodes during
           prostatectomy to ascertain lymph node status.

        -  A prior imaging agent for detecting lymph node involvement, dextran coated ultrasmall
           superparamagnetic iron oxide particles (USPIO), also known as Ferumoxtran-10 (Combidex ,
           AMAG Pharmaceuticals, Inc. Lexington, MA, US) was shown to localize lymph node
           metastases with much greater accuracy than unenhanced MRI. Although a large study in
           lymph node imaging in prostate cancer was successfully conducted using ferumoxtran-10,
           the FDA Advisory Panel did not recommend broad use approval of this agent.

        -  A derivative of ferumoxtran-10, Ferumoxytol (Feraheme AMAG Pharmaceuticals, Inc.
           Lexington, MA, US) has been approved for iron replacement therapy. It is a semisynthetic
           carbohydrate coated, magnetic iron oxide preparation. This compound is taken up by
           normal lymph nodes, excluded from malignant nodal tissue. A single study of Ferumoxytol
           enhanced MRI demonstrated some efficacy of this agent at 24 hours but only one dose was
           used, MRI at later time points was not performed.

        -  Initial results of the NCI trial (11-C-0098) revealed that using the dose of 7.5 mg/kg
           Fe is safe and it yields a more homogenous and accurate signal changes in benign lymph
           nodes in comparison with the 4 and 6 mg/kg Fe doses. However, utility of this initial
           result could not be validated in depiction of signal change difference between benign
           and malignant lymph nodes with prostate cancer metastases.

      Primary Objective

      -To determine the optimal dose of Ferumoxytol for enhancing lymph nodes in patients with
      prostate cancer.

      Eligibility

        -  Subject must be male and be (Bullet)18 years old.

        -  Subject must have a documented diagnosis of prostate cancer.

           --Those enrolling in the lymph node involvement subgroup must have imaging evidence of
           lymph node involvement (with a size of greater than or equal to 1.5cm)

        -  Eastern Cooperative Oncology Group Performance score of 0 to 2.

        -  Subjects must be scheduled to undergo prostatectomy and nodal dissection for presumed
           prostate cancer.

      Design:

        -  Subjects with prostate cancer scheduled for prostatectomy at the NIH Clinical Center
           will undergo pre-injection, 24, 48 (optional) hours post-Ferumoxytol injection MRI
           consisting of T1 weighted (W), T2W and T2*W MRI at 3 Tesla magnet.

        -  In the dose finding cohorts, each dose (4mg/kg Fe, 6mg/kg Fe, 7.5mg/kg Fe) will have an
           equal number of patients (estimated enrollment will be 5 evaluable patients for each
           group, making a total of 3x5=15 patients) will be enrolled sequentially. In the lymph
           node involvement cohort, 5 evaluable subjects will be enrolled.

        -  Subjects in the dose finding cohorts will undergo clinically indicated prostatectomy,
           nodal dissection for prostate cancer; histology of resected lymph nodes will be
           correlated with imaging.

        -  Subjects in the lymph node involvement cohort may be scheduled to undergo prostatectomy
           and nodal dissection or core needle biopsy of the lymph node(s) as part of their
           clinical work-up and histology of resected or biopsied lymph nodes will be correlated
           with imaging.
    

Intervention name(s): Ferumoxytol
Intervention type(s): Drug
Intervention description(s): All subjects will undergo pre-injection, 24, 48 hours post-Ferumoxytol injection (dose of 7.5mg/kg Fe) MRI consisting of T1 weighted (W), T2W and T2*W MRI in a 3 Tesla magnet. Additionally, all subjects will undergo pre-injection, 24 hours, 48 hours post-Ferumoxytol injection (dose of 7.5mg/kg Fe) ultrasound.
Intervention MeSH terms: Ferrosoferric Oxide
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Non-Cutaneous Malignancy; Prostatectomy; Metastatic Prostate Cancer; Imaging Study; Magnetic Resonance Imaging; Prostate Cancer