PNU 214936 IN ADVANCED ADENOCARCINOMAS OF THE BREAST

这是一项针对表现良好的转移性乳腺癌患者的开放标记、I期、重复给药、剂量递增的研究。患者将接受连续四天每天一次三小时的PNU-214936输注，以评估不良事件，评估对治疗的免疫学反应，并测量药代动力学参数。PNU-214936的DLTS和MTD将在最初的治疗周期中进行评估。根据一个持续调整的统计模型，考虑到基线抗SEA水平以及以前患者发生DLT的情况，将在后续患者中进行剂量递增。为了确保安全，新患者的剂量永远不会超过以前患者最高安全剂量的两倍。所有患者将在第一次输液后第11天和第28天接受评估，那些在第28天表现出肿瘤反应或病情稳定的患者可能会接受第二个为期4天的PNU-214936治疗周期。患者将在第56天、84天和此后每56天进行进一步评估，直到发现肿瘤进展的证据。

This is an open-label, phase I, repeated-dose, dose-escalation study in patients of good performance status with metastatic breast cancer. Patients will be treated with one daily three-hour infusion of PNU-214936 for four consecutive days to evaluate for adverse events, to assess immunologic response to treatment and to measure pharmacokinetic parameters. DLTs and MTD of PNU-214936 will be evaluated in this initial treatment cycle course. Dose escalations will proceed in successive patients based on a continuously adjusted statistical model that takes into account baseline anti-SEA levels as well as the occurrence of DLT in prior patients. To ensure safety, the dose in a new patient will never be more than double the highest safe dose given to any prior patient. All patients will be evaluated on Days 11 and 28 following the first infusion and those patients who demonstrate either a tumor response or stable disease at Day 28 may have a second 4-day treatment cycle with PNU-214936. Patients will be further evaluated at Day 56, 84 and every 56 days thereafter until evidence of tumor progression.