OT3-01-19: Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases.
Authors: Higgins DM , Childs J , Parker S , Disis ML , Salazar LG 
Published: June 2012

Abstract
Background
Breast cancer (BC) cutaneous lesions present as local chest wall recurrence or as isolated sites of metastatic disease. The treatment of cutaneous lesions is challenging and includes chest wall resection, local radiation therapy, and/or salvage chemotherapy which is not curative, associated with significant morbidity, and results in overall response rates of 20–30%. Thus, investigation of novel treatment strategies is warranted. This study incorporates multimodality treatment with topical imiquimod, a TLR-7agonist which generates an immune signal similar to that of pathogenic bacteria and Abraxane, a conventional systemic chemotherapy with potential immunostimulatory effects. Combined, these two agents provide local and systemic strategies which are potentially synergistic; and more effective than as single-agents in treating and controlling cutaneous disease.
Trial design: A Phase II single arm, non-randomized study. Patients will be sequentially enrolled and receive a maximum of 3 treatment cycles. A treatment cycle consists of topical imiquimod daily to target lesions for 4 days/week for 4 weeks in addition to Abraxane on Days 1, 8, and 15 every 28 days. Toxicity will be evaluated weekly during treatment then monthly for four months. Defined lesions are assessed at baseline and monthly. Skin biopsies are obtained pre and post treatment for histologic analysis and RT-PCR analysis of a 7 IFN-related gene signature previously associated with tumor inhibition. Immunity to BC antigens and serum TGF-β levels are also evaluated.
Aims: To evaluate the safety and anti-tumor effects of chemoimmunotherapy with topical imiquimod and Abraxane.
Eligibility criteria: Patients with progressive or relapsed BC after standard therapy who 1) have measurable cutaneous metastatic lesions, 2) are at least 7 days from last chemotherapy, 30 days from local radiotherapy and/or systemic steroids, 3) have adequate blood counts and 4) no history of active autoimmune disease. Bisphosphonates, trastuzumab, and/or hormonal therapy is allowed.
Statistical methods: Antitumor activity of target lesions will be assessed per modified WHO criteria. Complete response (CR)-complete clearance of lesions; Partial response (PR) ≥ 50% decrease in lesion size; Stable disease (SD) &lt; 50% decrease in lesion size; Progressive disease (PD) increase in ≥ 25% lesion size). Historical overall response rates (ORR) with second and third line salvage chemotherapy range from 20–30%, with CR rates less than 2%. Based on these numbers, an ORR of 50% or a CR rate of 10% will be used as benchmarks for success (i.e., ≥8 responses or ≥2 CRs among 15 patients (observed ORR of ≥ 53% or observed CR rate of ≥ 13%) to consider the treatment worthy of further study. As a measure of the precision of the estimate of ORR achievable with 15 patients, if the response rate is 60%, we will be 80% confident that the observed RR is within 0.16 of the true RR with 15 patients treated. Toxicity will be evaluated by CTCAE v. 3.0 and descriptive statistics will be used to summarize changes from baseline and for reporting of immunological parameters.
Accrual: 10 patients received treatment with a target accrual of 15.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-19.