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

Conditions: Breast Cancer

Summary: the purpose of this phase i/ii study is to evaluate the safety and clinical activity of radioiodide (131i-) as a novel targeted therapy for metastatic breast cancer that overexpresses functional na/i symporter. the study will enroll patients with metastatic breast cancer who have had clinical and/or radiographic evidence of disease progression on prior hormonal and/or chemotherapy.

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.

Eligibility criteria:
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 \ 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.

Keywords: metastatic breast cancer