Biomarker Correlates of Hypoxia in Metastatic Melanoma

A pilot phase II imaging study to determine hypoxia in melanoma.

About 16 - 24 hours before surgery, participants will be asked to come to the study center
to take the investigational agent oral pimonidazole (pimo) by mouth. Pimo is a substance
that is able to enter tissue when there are low levels of oxygen present (hypoxia). When the
tissue is removed and visualized under a microscope, the amount of pimo present is related
to the amount of oxygen in that part of the tissue. The dose of pimo given to the
participant will depend on their weight (13 mg pimo/kg body weight).

After surgery, a sample of the participant's tumor tissue will be viewed by doctors under a
microscope to determine the amount of pimo present.

Inclusion Criteria:

- Must be 18 years or older with a histological diagnosis of locally advanced,
recurrent or metastatic melanoma and be scheduled for clinically indicated surgical
removal of one or more melanoma tumors. Additionally, patients must have a resectable
tumor nodule ≥1 cm^3 (i.e., either a spherical tumor at least 1.0 cm in diameter or a
tumor measuring at least 1x1x1 cm). Prior biopsy is not required for study
participation.

- Not pregnant or nursing (as confirmed by serum pregnancy test if the patient is a
woman of child-bearing potential). Participants must agree with use birth control for
30 days following pimonidazole administration.

- Adequate kidney and liver function as assessed by laboratory studies

- Must be able to undergo magnetic resonance imaging (MRI) scans

- Capable of providing informed consent and demonstrate a willingness to comply with
all the study procedures and visits

- Eastern Cooperative Oncology Group (ECOG) score of 0 -1

Exclusion Criteria:

- Women who are pregnant or breastfeeding

- Patients who are contraindicated for MRI or gadolinium contrast agents due to:

- Presence of metallic objects or implanted medical devices in body (i.e., cardiac
pacemaker, aneurysm clips, surgical clips, prostheses, skin staples, implanted
prostheses, artificial heart valves with steel parts, metal fragments, shrapnel,
or other metal implants that would contraindicate MRI)

- Sickle cell disease

- Renal failure with estimated glomerular filtration rate (eGFR) < 30
mL/min/1.73m^2 based upon serum creatinine

- Weight greater than 350 lbs (the weight limit for the MRI)

- Patients with known, active (i.e. not adequately treated with curative intent)
malignancies other than melanoma

- Presence of any other co-existing condition which, in the judgment of the
investigator, might increase the risk to the participant