Efficacy and tolerability of BP-C1 in metastatic breast cancer: a Phase II, randomized, double-blind, and placebo-controlled Thai multi-center study

Kritiya Butthongkomvong, Nilubol Raunroadroong, Sirikul Sorrarichingchai, Isaraporn Sangsaikae, Vichien Srimuninnimit, Henrik Harling, Stig Larsen, Kritiya Butthongkomvong, Nilubol Raunroadroong, Sirikul Sorrarichingchai, Isaraporn Sangsaikae, Vichien Srimuninnimit, Henrik Harling, Stig Larsen

Abstract

Aims: The aim of this study was to compare the efficacy and tolerability of BP-C1 vs equal-looking placebo in metastatic breast cancer.

Materials and methods: A randomized, double-blind, placebo-controlled multi-center study with a semicross-over design was performed. Sixteen patients received daily intramuscular injection of 0.035 mg/kg bodyweight of BP-C1 and 15 patients received equal-looking placebo for 32 days. After 32 days, the placebo patients crossed to BP-C1 with the last observation in the placebo period as baseline. The status of receptors including estrogen receptor (ER), progesterone receptor (PtR), and human EGF receptor 2 (HER2) was analyzed prior to inclusion in the study. Thoracoabdominal CT scan was blindly analyzed by the same independent radiologist in accordance with the RECIST criteria 1.1. Toxicity was assessed according to the NCI Bethesda Version 2.0 (CTC-NCI), and the quality of life (QOL) was assessed according to European Organization for the Research and Treatment of Cancer QOL-C30 and QOL-BR23.

Results: The sum of target lesion diameters (sum lesions) after 32 days of treatment increased by 8.9% (P=0.08) in the BP-C1 arm compared to 37.6% (P<0.001) in placebo patients. Twelve of the 15 placebo patients subsequently had BP-C1 treatment. The increase in sum lesions was 3.5% in these patients. The sum of CTC-NCI was increased 18.7% in the BP-C1 arm (P=0.38) compared to 50.9% (P=0.04) in placebo patients. Four mild/moderate adverse events (AEs) present in BP-C1. Two mild/moderate AEs and one severe AE present in placebo. The QOL benchmarks "breast cancer problems last week", "sexual interest and activity last 4 weeks", and "breast cancer-related pain and discomfort last week" were stable in the BP-C1 arm but deteriorated in placebo patients. The sum lesions increased significantly in ER+ (P=0.02) and PtR+ (P=0.03) but not in HER2+. The increase in sum lesions significantly decreased (P=0.02) with an increasing number of negative receptors.

Conclusion: A total of 32 days of BP-C1 treatment inhibited cancer growth and was well tolerated with few and mainly mild AEs. The efficacy of BP-C1 was superior in receptor-negative patients.

Clinicaltrialsgov identifier: NCT03603197.

Keywords: BP-C1; benzene-polycarboxylic acid complex; breast cancer; hormone receptors; low-dose cisplatin; randomized double-blind; stage IV.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The development in sum of the largest diameters of target lesions in millimeter. Notes: The results are expressed by mean values with 95% CIs illustrated by columns. The horizontal line crossing the columns shows the mean values. The green column shows BP-C1, and the yellow column shows placebo. The blue column shows the development in the 12 patients after switching from placebo to BP-C1.
Figure 2
Figure 2
The development in sum of CTC-NCI toxicity score from screening to Days 16 and 32 in the BP-C1 group and the placebo group. Notes: The results are expressed by mean values with 95% CIs illustrated by columns. The horizontal line crossing the columns shows the mean values. The green column shows BP-C1, and the yellow column shows placebo.

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