A Multi-center, Randomized, Double Blind, Placebo Controlled Clinical Trial to Evaluate the Efficacy of Intratumoral Injection TD-B10 in Dogs with Perianal Gland Tumors

TD-B10 is a formula composite of which the principal component is metformin, a biguanide hypoglycemic agents for type 2 diabetes treatment. Metformin is known to have antineoplastic activity by activating the AMPK/mTOR pathway. Necrosis induced by tumor necrosis factor (TNF) is also considered an important part in the TD-B10 antitumor activity. The aim of this study is to determine the treatment efficacy in canine perianal gland tumors also the safety and feasibility of TD-B10 intratumoral injection in small animal cancer patients. Dogs with histopathologically confirmed perianal gland tumors are stratified and randomly divided into two groups. The tumors will receive either TD-B10 injection or placebo control once daily on weekdays for two consecutive weeks for total of 10 injections. The primary end point is the response rate and the tumor regression rate at the end of the 4-weeks follow-up period. A total of 26 dogs were recruited. The tumor regression rate in treatment group (n=14) was 45.16 ± 42.87% compared with -6.15 ± 45.64% for placebo group (n=12) (P=0.0168). The objective response rate in treatment group was 57.14% (8/14; 2 CR, 6 PR) compared with 8.33% (1/12; 1 PR) for placebo group (P=0.0145). The tumor regression rate of TD-B10 group was higher than the placebo group despite the patients’ breed, tumor volume, clinical stage and multiple factors. The toxicities were mostly limited to grade I to II where injection site reactions, pain and gastrointestinal toxicities were most commonly observed. The result of this study demonstrated that TD-B10 has significant anti-tumor activity and can evoke tumor regression in canine perianal tumors.