Ferumoxytol-Enhanced MRI in Imaging Lymph Nodes in Patients With Locally Advanced Rectal Cancer

PRIMARY OBJECTIVES:

I. To determine feasibility of administering ferumoxytol and obtaining ferumoxytol enhanced
magnetic resonance (MR) images in patients with resectable locally advanced rectal cancer
with enlarged or suspicious lateral pelvic lymph nodes before starting neoadjuvant
chemoradiation therapy and again before total mesorectal excision.

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 total mesorectal excision.

II. To compare the sensitivity and specificity of ferumoxytol enhanced MR imaging in
assessment of pathological lymph nodes with those of non-USPIO-MRI and positron emission
tomography-computed tomography (PET-CT).

OUTLINE:

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

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

Inclusion Criteria:

- Pathologically confirmed, locally advanced, malignancy of the rectum; based on
multi-disciplinary tumor board discussion, patients are candidates for tri-modality
treatment

- Stage T1-4bN1-2, by the American Joint Committee on Cancer (AJCC) 7th edition, based
on the following minimum workup:

- CT chest/abdomen with contrast

- MRI pelvis with contrast

- PET/CT of the whole-body or skull base to mid-thigh

- Subjects must have had no prior therapy for cancer of the rectum

- Members of all races and ethnic groups will be included

- 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 AJCC 7th edition stage TxN0 and M1 disease

- Prior systemic chemotherapy for rectal 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 abdominopelvic radiation or radiation for rectal 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 low anterior resection or abdominoperineal resection

- 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; 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 concurrent clinical diagnosis of evidence of active iron overload
defined by the following 1) ferritin >= 250 ng/mL in men or >= 200 ng/mL in women AND
2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as
percent, >= 45%

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible

- Patients with renal insufficiency; glomerular filtration rate (GFR) < 60

- Adult patients who require monitored anesthesia for 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 as determined by either a prior
diagnosing physician or at review at initial consultation; these disease entities do
not have formal associated lab values and are thus a clinical diagnosis by the prior
aforementioned physician