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，重组人白细胞介素-12 （rhIL-12）通过留置IP导管腹腔注射，起始剂量为3ng /kg，持续8周。患有穆勒蛋白癌、腹膜间皮瘤或胃肠道恶性肿瘤的成年腹部癌患者，如果符合入组标准，将有资格。这项研究的长期目标是利用rhIL-12为这些患者开发有效的治疗方法。假设IP rhIL-12会增强由穆勒蛋白癌或胃肠道（GIT）恶性肿瘤引起的腹膜癌患者的抗肿瘤反应。具体目的是：1)确定iprhil -12的定性和定量毒性、毒性可逆性和每周给药的最大耐受剂量，测定iprhil -12的血清、腹膜浓度和药代动力学；2)通过研究T细胞活化和分化标志物、T细胞因子和自体肿瘤细胞的细胞毒性，确定IP rhIL-12对T细胞功能的影响；3)检测IP rhIL-12是否调节HLA I类、II类抗原、TGFB、IP-10、VEGF在腹膜癌细胞上的表达；4)测定腹膜液细胞病理学和DNA流式细胞术变化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.