Phase 1b breast cancer prevention clinical trial of 9cUAB30 administered prior to surgical resection

We performed a phase Ib clinical trial in participants with breast carcinoma evaluating the effects of the novel rexinoid 9cUAB30 orally for 14-28 days prior to surgical resection. Twenty-seven female volunteers (mean±S.D. age 63±10 years) newly diagnosed with breast cancer awaiting surgery as their initial treatment received 9cUAB30 once daily (240 mg for first 5 participants and 160 mg for the subsequent 22 participants) for 13-25 days. Comparison of breast tissue proliferation (Ki-67) at baseline and end of study revealed no significant change with results similar to participant-matched historical control samples. Secondary analysis of tissue apoptosis (Cleaved Caspase 3) observed an increase from baseline to end of study but when compared to changes exhibited by matched to historical controls, no difference was observed. Exploratory analysis of participant tissue samples by nCounter molecular profiling observed increased cytokine and decreased proliferation marker gene expression. Assessment of circulating dendritic cells demonstrated an increase in type 1 monocytic and a decrease in type 2 plasmacytic cells. 9cUAB30 plasma concentrations day of surgery were 349 ± 204 ng/ml (range 66-873). Most participants had grade 1-2 adverse events with the most common being hypertension, headache and gastrointestinal- and skin-related symptoms. Laboratory analysis observed a small but significant increase in total and LDL serum cholesterol (p<0.001). In this phase Ib clinical trial, 9cUAB30 was well tolerated with mild rexinoid-related side effects, no measurable effect upon breast tissue proliferation but encouraging exploratory effects on gene expression and circulating immune effector cells at relatively high daily rexinoid dosing.