Study of TH-302 Monotherapy as Second-line Treatment in Advanced Biliary Tract Cancer
Status:
Completed
Trial end date:
2017-10-01
Target enrollment:
Participant gender:
Summary
Biliary tract cancer is relatively rare cancer, with generally poor prognosis. In
metastatic/recurrent biliary tract cancer, the most commonly used 1st-line chemotherapy is
gemcitabine+cisplatin combination. However, there is no standard 2nd-line chemotherapy and
there is no validated targeted therapeutic agent, even though this tumor harbors diverse
genetic characteristics.
TH-302 (1-methyl-2-nitro-1H-imidazole-5-yl)methyl N,N'-bis(2-bromoethyl) diamidophos-phate is
a nitroimidazole-linked prodrug of a brominated version of isophosphoramide mustard (Br-IPM).
When exposed to hypoxic conditions, TH-302 is reduced at the nitroimadazole site of the
prodrug by intracellular reductases leading to the release of Br-IPM. Br-IPM can then act as
a DNA crosslinking agent. In areas of normoxia, TH-302 remains intact as a prodrug and
toxicity is minimized. In addition, preclinical data suggest that after activation, the
active moiety may diffuse to areas outside the hypoxic region, demonstrating a "bystander"
effect and possibly exhibiting additional anti-tumor activity.
It is well known that biliary tract cancer is hypovascular tumor, so it contains large
hypoxic area in the tumor. Therefore it would be worthy to test TH-302 in biliary tract
cancer.
This study is a phase II study of TH-302 monotherapy as second-line treatment in advanced
biliary tract cancer, to investigate efficacy and safety of TH-302 monotherapy.
Phase:
Phase 2
Details
Lead Sponsor:
Seoul National University Hospital
Collaborators:
Merck Serono International SA Threshold Pharmaceuticals