Ferumoxytol-Enhanced MRI in Adult/Pedi Sarcomas

Ferumoxytol-Enhanced Magnetic Resonance Imaging (MRI) in Pediatric and Adult Patients With Malignant Sarcoma: A Two-part Pilot Study for Safety and Efficacy in the Pediatric and Adult Populations

This research study is a pilot study to evaluate a new contrast agent, ferumoxytol, for the purpose of imaging lymph node metastases in patients with soft tissue sarcoma. This contrast agent is an investigational drug. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved ferumoxytol for this use. This drug has been used to image adults with other forms of cancer, however, it has only been used to image a small number of pediatric patients. Ferumoxytol has never been used to image sarcoma.

Study Overview

• Status: Withdrawn
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Ferumoxytol

Detailed Description

Before the research starts you will undergo some screening procedures to confirm that you are eligible to participate in the study. These include a medical history, blood tests and an electrocardiogram.

After we confirm taht you are eligible for this study you will undergo the following. We estimate that you will be on the study for approximately two to three weeks.

Baseline MRI of the tumor site and draining lymph nodes: Whether you are on the study or not you will have a baseline MRI which involves the use of a standard contrast agent called gadolinium. This imaging test is considered the standard of care and is the method by which doctors determine tumor location and spread. This MRI is NOT part of the study.

Ferumoxytol Infusion: You will receive this study drug the same day as your baseline MRI; if you already had your baseline MRI, this medication can be given intravenously (i.e. directly into the vein) at your next clinical visit. It can likewise be given through a central line. You will be observed during the infusion and 30 minutes after the infusion to ensure that you do not have an allergic or adverse reaction to the medication.

Repeat MRI of the tumor site and draining lymph nodes: Three to five days after receiving ferumoxytol, you will undergo a repeat MRI. You will not require any additional contrast prior to this imaging study. This MRI is part of the study.

Lymph Node Biopsy: You will be undergoing a lymph node biopsy whether or not you are on the study. This will occur approximately a week after your study MRI. This is a surgical procedure that involves removing one or a few lymph nodes in the region of your tumor and studying them under a microscope to determine whether they contain signs of microscopic cancer spread. Your surgeon will explain this procedure to you in more detail.

We anticipate that your clinic visit for ferumoxytol will take approximately an hour. MRI tests, on average, likewise take approximately an hour to complete.

After you have completed the study MRI and lymph node biopsy, you will require one additional blood test to measure blood iron levels. We measure iron levels because ferumoxytol is comprised of an iron core. This iron is similar to that in oral iron supplements and can cause your blood iron levels to temporarily increase. Because we are trying to determine whether this contrast agent will be useful, you will not receive teh results to the study MRI. If however, lymph nodes are found to be positive for disease, your treatment plan may change to address this.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• New diagnosis of soft tissue sarcoma, who will undergo lymph node biopsy
• Able to tolerate MRI scan without sedation/anesthesia
• Greater than or equal to 12 years of age

Exclusion Criteria:

• Previous therapy other than biopsy or surgical resection of the primary tumor
• Pregnant or breastfeeding
• Receipt of other iron-oxide based nanoparticle therapy within 4 weeks of scans
• History of allergic reaction to compounds of similar composition to ferumoxytol
• Known diagnosis of hemochromatosis, mitochondrial disorder or iron overload
• Invasive bacterial infection
• Known history of contrast sensitivity
• Braces or metal heart valve that may interfere with MRI, surgical clips, a pacemaker, piercings that cannot be removed, or any other indwelling metal device that might interfere with MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanoparticle enhanced MRI	Drug: Ferumoxytol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility and sensitivity of nanoparticle-enhanced MRI	To determine the feasibility and evaluate the sensitivity of using nanoparticle-enhanced MRI in detecting lymph node metastases in pediatric and adult soft tissue sarcoma patients with clinically palpable or radiographically concerning lymph nodes, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard	4 years
Sensitivity of nanoparticle-enhanced MRI in occult lymph node metastases	To evaluate the sensitivity of nanoparticle-enhanced MRI in detecting occult lymph node metastases in pediatric and adult patients with soft tissue sarcoma, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of ferumoxytol in pediatric patients	The safety of ferumoxytol in pediatric patients will be assessed by the proportion of patients who experience at least one dose limiting toxicity (DLT). DLT refers to toxicities experienced after the start of the drug infusion; they are based on the Common Terminology Criteria for Adverse Events version 4.0.	4 years
Sensitivity of conventional MRI vs. nanoparticle enhanced MRI	To evaluate the sensitivity of conventional MRI in detecting the presence of lymph node abnormalities in pediatric and adult patients with soft tissue sarcoma, and to compare this to the sensitivity of nanoparticle-enhanced MRI. The sensitivity of nanoparticle-enhanced MRI will be descriptively compared to the sensitivity of conventional MRI, where in each case the histological confirmation of lymph node involvement is the "standard of truth." For conventional MRI, sensitivity will be measured by the number of patients in whom at least one lymph node abnormality was detected by conventional MRI, as determined by the primary radiologist, divided by the total number of evaluable patients.	4 years
Compare inter-reader variability in the interpretation of nanoparticle MRI scans	To determine inter-reader variability in the interpretation of nanoparticle MRI scans by two independent radiologists. The comparison will be made between each central review radiologist's assessment of whether or not a given patient has a positive lymph node.	4 years
Retrospective central pathology review	To perform a retrospective central pathology review to determine inter-pathologist interpretation of positive lymph nodes. This too will be done through comparison of each central review pathologist's assessment of whether or not a given patient has a positive lymph node.	4 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Allison O'Neill, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: July 28, 2012
• First Submitted That Met QC Criteria: August 8, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Newly diagnosed
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: 11-254