A Clinical Trial Evaluating the Safety and Clinical Activity of Radioiodide (131I-) as a Novel Targeted Therapy for Metastatic Breast Cancer That Overexpresses Functional Na/I Symporter

The primary objectives of the study are as follows:

1. To evaluate the feasibility of using 124I- PET/CT scans to identify patients whose
metastatic lesions accumulate radioactive iodide and therefore are candidates for 131I-
therapy.

2. Determine the frequency of iodide (124I) enriching metastatic breast cancer.

3. Evaluate the safety and clinical activity of one-time 131I treatment to patients who
screen positive on 124I- PET/CT screening, positivity is defined as calculated iodide
enrichment that will allow delivering 2000 cGy or more radiation to one or more
metastatic lesion by administering up to 200mCi 131I-.

The secondary objectives of the study are as follows:

1. To investigate a correlation between NIS expression in tumor tissue with 124I- uptake on
screening PET/CT scan

The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of
I- treatment. The maximum tolerated dose will be used in the Phase II efficacy assessment
which will follow a Simon's optimal two-stage design. The primary efficacy measure is
objective tumor response rate (CR or PR) with targeted activity level of > 20% response rate.

The study will be terminated for futility if no tumor response is seen in the first 12
patients. If futility criteria is not met, a total of 37 eligible patients will be enrolled
in the Phase II portion. If 4 or more responses are seen after 37 patients were evaluated,
then the investigators will conclude that the regimen warrants further study.

Inclusion Criteria:

Each patient must meet all inclusion criteria in order to be considered for enrollment:

- Histologically confirmed breast cancer with clinical and/or radiological evidence of
measurable or evaluable metastatic disease by Response Evaluation in Solid Tumors
(RECIST) 1.1.

- Life expectancy ≥12 weeks.

- Radiologic or clinical evidence of disease progression on prior hormonal and/or
chemotherapy

- There is no restriction on the number of prior lines of therapy.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of < 2.

- Full recovery to Grade ≤ 2 from any prior side effects of prior therapy for cancer
including radiation therapy, chemotherapy, and/or immunotherapy.

- Adequate bone marrow function defined as white blood cells (WBCs) ≥ 3.0 × 109/L,
neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.

- Adequate renal function defined as serum creatinine < 1.5 mg/dL or creatinine
clearance (GFR) > 40 mL/min calculated using the following formula: GFR = 175 x Serum
Cr-1.154 x age-0.203 x 0.742 (female) and x 1.212 (if patient is African American).

- Adequate liver function defined as AST, ALT ≤ 3 × upper limit of normal (UNL) in the
absence of liver metastasis and ≤ 5 × UNL with liver metastases; bilirubin < 1.5 ×
UNL; alkaline phosphatase ≤ 2.5 × UNL in the absence of liver metastasis and < 5 × UNL
in case of bone metastases.

- TSH, T3 and free T4 must be within normal range.

- The patient should not have had intravenous or intrathecal iodinated contrast agents
(IVP, CT with contrast, myelogram, angiogram) for 4 weeks prior to screening to their
124I- PET/CT scans and/or 131I- treatment.

- Patients with treated brain metastases are eligible if the brain metastases have
remained stable for more than 4 weeks after completing therapy to the brain.

- Normal urine or serum Beta-HCG in premenopausal women of childbearing potential

- Women of childbearing potential must agree to use effective contraception during the
treatment period and for at least 6 months after the last dose of 124I- and/or 131I-
as these agents interfere with radioactive iodide uptake

- Signed informed consent.

Exclusion Criteria:

- Concurrent anti-tumor treatment including radiation therapy, hormonal and
chemotherapy.

- Patients with symptomatic cardiac disease such as coronary artery disease, congestive
heart failure, or atrial fibrillation.

- Significant gastrointestinal abnormalities, including: ulcerative colitis, chronic
diarrhea associated with intestinal malabsorption, Crohn's disease, and prior surgical
procedures affecting absorption.

- Women who are nursing or pregnant.