IP RECOMBINANT HUMAN IL-12 IN PATIENTS WITH PERITONEAL CARCINOMATOSIS

该研究是一项单臂、非随机I期试验，通过留置IP导管以3 ng/kg的起始剂量腹膜内给予重组人白细胞介素-12（rhIL-12）8周。 如果符合入选标准，则患有苗勒兰癌、腹膜间皮瘤或胃肠道恶性肿瘤所致腹部癌转移的成人患者将有资格入选。 该研究的长期目标是使用rhIL-12为这些患者开发有效的治疗方法。 假设IP rhIL-12将增强由苗勒兰癌或胃肠道（GIT）恶性肿瘤引起的腹膜癌转移患者的抗肿瘤反应。 具体目的是：1）确定IP rhIL-12每周给药的定性和定量毒性和毒性可逆性以及最大耐受剂量，并确定IP rhIL-12的血清、腹膜浓度和药代动力学; 2）通过研究T细胞活化和分化的标志物来确定IP rhIL-12对T细胞功能的影响，T细胞细胞因子和自体肿瘤细胞毒性; 3）确定IP rhIL-12是否调节腹膜癌细胞上HLA I类和II类抗原、TGFB、IP-10和VEGF的表达; 4）确定腹膜液中的细胞病理学和DNA流式细胞术变化以及细胞因子的临床活性。

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, peritoneal mesotheliomas, 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.