A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer

Abstract

The purpose of this study was to determine the safety and maximum tolerated dose (MTD) of BZL101 (FDA IND# 59,521), an orally delivered aqueous extract from the herb Scutellaria barbata, in women with metastatic breast cancer (MBC). The trial was an open-label, phase 1B, multicenter, dose escalation study. Eligible patients had histologically confirmed breast cancer and measurable stage IV disease. The standard phase 1 "3 + 3" study design was used to determine the MTD. Primary endpoints were toxicity and MTD of BZL101. Secondary outcomes included efficacy based on RECIST criteria. A total of 27 women with a median of 2 prior chemotherapy treatments for metastatic disease were treated in four different dose cohorts. Grade 3 and 4 adverse events (AEs) were uncommon. Dose-limiting toxicities included the following: grade 4 AST elevation, grade 3 diarrhea, grade 3 fatigue, and grade 3 rib pain. Fourteen patients were evaluable according to Response Evaluation Criteria in Solid Tumors. Investigator assessment classified three patients with stable disease for >120 days (21%). One patient was on BZL101 for 449 days and remains stable for 700 + days. Independent radiology review identified three patients with objective tumor regression (>0% and <30%). The MTD was not reached, thus per protocol, the MTD was defined as the maximum administered dose of BZL101 40 g/day. In conclusion, oral administration of BZL101 was safe, well tolerated, and showed promising clinical evidence of anticancer activity in this heavily pretreated population of women with MBC.

BZL101, a phytochemical extract from theScutellaria barbataplant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype

“…18 We now demonstrate that BZL101 can affect expression levels of HER2 in human breast cancer cells in an early stage cancer cell phenotype.…”

“…Aqueous extracts of BZL101 contain several active anticancer compounds, 16 which are able to block glycolysis and induce cell death in a number of cancer cell lines, 17 and is well tolerated by metastatic breast cancer patients. 18 While the effect of BZL101 on the metabolic functioning of cancer cells has been studied, relatively little is known about how BZL101 regulates proliferative signaling and cell cycle control within human reproductive cancer cells. Virtually nothing is known about the BZL101 control of steroid and growth factor signaling pathways, which are both critical to the promotion and progression of reproductive cancers.…”

Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

“…completed Phase Ia and Ib clinical trials for treatment of metastasized breast cancer with encouraging results (Rugo et al, 2007;Perez et al, 2010). Along with its anticancer properties, S.…”

“…The traditional method of extracting TCM herbs by simmering in water was followed when making extracts of S. barbata for both Ia and Ib phases of BZL101's clinical trials (Rugo et al, 2007;Perez et al, 2010). However, during Phase Ib, a modified formulation using freeze-dried powdered drug with sweeteners and taste-masking excipients was introduced to increase patient adherence.…”

“…Western research has recently turned its attention to S. barbata as a possible source of anticancer compounds. An aqueous extract of the aerial parts of S. barbata named Bezielle (BZL101) was developed by Bionovo, a California-based biotechnology company, and completed Phase I clinical trials in the United States with favorable results (Rugo et al, 2007;Perez et al, 2010). Unfortunately, the developmental of this S. barbata-based medicine has been halted due to insufficient funding (Bionovo, 2015).…”