Ferumoxytol-Enhanced MRI in Imaging Lymph Nodes in Patients With Stage IIB-IIIC Esophageal Cancer

A Pilot Study Using a Novel Imaging of Lymph Nodes in Patients With Locally Advanced Esophageal Cancer Using Ferumoxytol Enhanced MRI

This pilot clinical trial studies how well ferumoxytol-enhanced magnetic resonance imaging (MRI) works in imaging lymph nodes in patients with stage IIB-IIIC esophageal cancer. Ferumoxytol is a form of very small iron particles that are taken up by cells in normal lymph nodes and may work better in imaging patients with esophageal cancer when paired with MRI.

Study Overview

• Status: Withdrawn
• Conditions: Stage IIB Esophageal Cancer AJCC v7; Stage III Esophageal Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7; Stage IIIC Esophageal Cancer AJCC v7
• Intervention / Treatment: Drug: Ferumoxytol; Procedure: Magnetic Resonance Imaging

Detailed Description

PRIMARY OBJECTIVE:

I. To determine feasibility of administering ferumoxytol and obtaining ferumoxytol enhanced magnetic resonance (MR) images in patients with resectable locally advanced esophageal cancer before starting neoadjuvant chemoradiation therapy and again before esophagectomy.

SECONDARY OBJECTIVES:

I. To collect detailed information about the location of ultrasmall superparamagnetic iron oxide (USPIO)-MRI detected lymph nodes prior to neoadjuvant chemoradiation therapy and again prior to esophagectomy.

II. To determine the sensitivity and specificity of ferumoxytol enhanced MR imaging in the assessment of pathologic lymph node involvement based on pathological findings at the time of esophagectomy.

OUTLINE:

Patients receive ferumoxytol intravenously (IV) over 15 minutes and then undergo ferumoxytol-enhanced MRI after 24-36 hours and before surgery at week 12.

After completion of study treatment, patients are followed up for 4-6 weeks.

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed, locally advanced, malignancy of the esophagus; the cancer may involve the stomach up to 5 cm; based on multi-disciplinary tumor board discussion, patients are candidates for tri-modality treatment

• Stage T1-4aN1-2, by the American Joint Committee on Cancer (AJCC) 7th edition, based on the following minimum workup:

  • Computed tomography (CT) chest/abdomen with contrast
  • Positron emission tomography (PET)/CT of the whole-body or skull base to mid-thigh
  • Patients must have regional adenopathy and have undergone endoscopic biopsy with endoscopic ultrasound (EUS)-proven peri-esophageal nodal involvement
• Subjects must have had no prior therapy for cancer of the esophagus
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• White blood cell count >= 3.0 K/cu mm
• Absolute neutrophil count >= 1.5 K/cu mm
• Platelets >= 100 K/cu mm
• Hemoglobin >= 8.0 g/dl (The use of transfusion or other invention to achieve Hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
• Serum ferritin < 2.0 X institutional upper limit of normal
• Woman of childbearing potential, a negative serum or urine pregnancy test
• Willingness to use adequate contraception for 12 months after completion of all therapy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Subjects with cervical or Siewert 3 esophageal carcinoma, that are recommended by the multi-disciplinary tumor board to have treatment other than tri-modality chemo-radiation therapy (RT) followed by esophagectomy
• Subjects with AJCC 7th edition stage TxN0, T4b, and M1 disease
• Prior systemic chemotherapy for esophageal cancer; prior chemotherapy for another malignancy is allowable as long as it has been > 2 years since completion of therapy for previous malignancy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol or other agents used in the study
• Prior chest radiation or radiation for esophageal cancer
• History of other malignancy in the past 2 years except non-melanomatous skin cancer, breast ductal carcinoma in situ (DCIS) and low-risk prostate adenocarcinoma
• Medical contraindications to esophagectomy
• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because chemoradiotherapy has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to the use of ferumoxytol as a contrast agent in the mother, breastfeeding should be discontinued if the mother receives ferumoxytol while nursing; men who are sexually active and not willing/able to use medically acceptable forms of contraception are also excluded from this study
• Subjects with multiple drug allergies and/or subjects who have had an allergic reaction to any intravenous iron replacement product or a known history of hypersensitivity to ferumoxytol
• Subjects with evidence of iron overload
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ferumoxytol
• Patients with renal insufficiency; glomerular filtration rate (GFR) < 60
• Adult patients who require monitored anesthesia for magnetic resonance imaging (MRI) scanning
• Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to gadolinium (Gd) contrast material
• Subjects with known hepatic insufficiency or cirrhosis

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: Diagnostic (ferumoxytol, MRI); Patients receive ferumoxytol IV over 15 minutes and then undergo ferumoxytol-enhanced MRI (Magnetic Resonance Imaging) after 24-36 hours and before surgery at week 12.	Drug: Ferumoxytol; Undergo ferumoxytol-enhanced MRI; Other Names: Feraheme; Ferumoxytol Non-Stoichiometric Magnetite; Procedure: Magnetic Resonance Imaging; Undergo ferumoxytol-enhanced MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Practical feasibility	Will be assessed by successful accrual objectively, as a percentage of all subjects enrolled. Accrual success will be measured in binary fashion; successful accrual is considered a patient that enrolls and completes the entire trial. All other eligible patients will be considered an accrual failure. Practical feasibility will be considered a success if greater than 50%.	Up to 18 weeks
Technical feasibility of ultrasmall superparamagnetic iron oxide (USPIO) - magnetic resonance imaging (MRI) of the chest	Will be evaluated in a descriptive manner. Image quality, readability (i.e. the ability for diagnostic radiologist to make an appropriate diagnostic conclusion, completion of ferumoxytol infusion, data acquisition, and completion of MR protocol.	Up to 18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of USPIO - MRI	Accuracy, which is defined as the percentage of all patients or lymph nodes in which MRI with ferumoxytol correctly predicted the presence or absence of metastatic tumor, will be calculated.	Up to 18 weeks
Reason for accrual failure	Descriptive statistical analysis of accrual failure will be conducted, counting the number of subjects who fail to complete the entire trial and the reasons for failure.	Up to 18 weeks
Report location and enhancement patterns on USPIO - MRI		Up to 18 weeks
Sensitivity and specificity of MRI imaging for all lymph nodes	Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant chemoRT will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from positron emission tomography (PET)/computed tomography (CT) findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.	Up to 18 weeks
Sensitivity and specificity of PET/CT imaging	Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant chemoRT will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from PET/CT findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.	Up to 18 weeks

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: Alexander Guimaraes, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): August 19, 2021
• Study Completion (Actual): August 19, 2021

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: IRB00012071 (Other Identifier: OHSU Knight Cancer Institute); NCI-2016-01093 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No