IP RECOMBINANT HUMAN IL-12 IN PATIENTS WITH PERITONEAL CARCINOMATOSIS

该研究是一项单臂、非随机的重组I期临床试验

The study is a single-arm, non-randomized Phase I trial of recombinant human interleukin-12 (rhIL-12) administered intraperitoneally via an indwelling IP catheter for 8 weeks at a starting dose of 3 ng/kg. Adult patients with abdominal carcinomatosis from Mullerain carcinomas or gastrointestinal malignancies will be eligible if they meet entry criteria. The long-term goal of the study is to develop effective treatment for these patients using rhIL-12. The hyposthsis is that IP rhIL-12 will enhance antitumor responses in patients with peritoneal carcinomatosis caused by Mullerain carcinomas or gastrointestinal tract (GIT) malignancies. The specific aims are 1) to determine the qualitative and quantitative toxicity and reversibility of toxicity and the maximum tolerated dose of IP rhIL-12 given on a weekly schedule, and to determine the serum, peritoneal concentration and pharmacokinetics of IP rhIL-12; 2) to determine the effect of IP rhIL-12 on T cell functions by studying markers of T-cell activation and differentiation, T-cell cytokines and autologous tumor cell cytotoxicity; 3) to determine whether IP rhIL-12 modulates expression of HLA class I and class II antigens, TGFB, IP-10 and VEGF on peritoneal carcinoma cells; 4) to determine cytopathologic and DNA flow cytometry changes in peritoneal fluid and clinical activity of the cytokine.