IP RECOMBINANT HUMAN IL-12 IN PATIENTS WITH PERITONEAL CARCINOMATOSIS

这项研究是一项单臂非随机I期重组人试验 人白细胞介素12(rhIL-12)经腹膜腔内注射 IP导管留置8周，起始量为3 ng/kg。成虫 由Mullerain癌或其他原因引起的腹部癌病 胃肠道恶性肿瘤如果符合入选条件将符合条件 标准。这项研究的长期目标是开发有效的 使用重组人白介素12治疗这些患者。先天性巨结肠就是IP 重组人IL-12可增强腹膜癌患者的抗肿瘤反应 Mullerain癌或胃肠道引起的癌病 (Git)恶性肿瘤。具体目标是：1)确定定性的 以及定量毒性和可逆性毒性的最大 每周给药一次的耐受量，并确定 注射用重组人白介素12的血药浓度和药代动力学 通过研究确定ip rhIL-12对T细胞功能的影响 T细胞活化和分化的标志物，T细胞细胞因子和 自体肿瘤细胞的细胞毒作用；3)确定ip rhIL-12 调节HLAI、II类抗原、TGFb、IP-10和 血管内皮生长因子对腹膜癌细胞的影响；4)细胞病理学和DNA检测 腹腔液中的流式细胞术变化及临床活动性 细胞因子。

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.