BIOEQUIVALENCE COMBINATION 776C85/5FU PILL & INDIVIDUAL 776C85 & 5FU PILL

目的：这是一项I期，开放标签，上升，多剂量的研究 旨在描述安全概况并确定最大- SCH-66336给药的耐受量和剂量限制毒性 口服给患有晚期癌症的成年患者。SCH 66336是一种强大的， 法尼基蛋白转移酶的特异性抑制剂。这个转移酶是 是激活ras蛋白所必需的，当突变时，ras蛋白经常 在人类癌症中发现。因此，SCH 66336代表了一个新的类别 抗肿瘤化合物。它是由先灵葆雅公司开发的，还没有 但已经在人体上进行了测试。 方法：符合I期试验条件的患者将符合以下条件 组织学证实的无骨髓的实体瘤恶性肿瘤 介入，没有传统的治疗方法可用。不再 允许对晚期疾病进行两种之前的化疗方案。 在每个剂量水平上，受试者将接受单剂量的SC 66336 之后进行24小时观察期(仅限L周期)。研究对象将 然后连续13天每天两次接受SC 66336。在每个剂量下 水平，药代动力学评价将在第1天和第14天进行。 病人将被安置在临床研究单位进行监测和 首剂药代动力学和日间重复药代动力学 14.每个剂量水平将治疗一名患者，直到DLT 观察到的。如果在前28天观察到II级毒性(非DLT) 几天后，将在该剂量水平上再招募2名受试者。如果有 三名患者中有三名患者患有非DLT，那么一名患者将继续病情升级 患者在每个剂量水平。如果2名或3名受试者患有非DLT，则剂量 升级计划将更改为每个剂量级别3名受试者。 在没有疾病的情况下，患者可以继续服用SC 66336 进展(28天周期)。

PURPOSE: This is a phase I, open-label, rising, multiple-dose study designed to characterize the safety profile and determine the maximally- tolerated dose and dose-limiting toxicity of SCH 66336 when administered orally to adult patients with advanced cancer. SCH 66336 is a potent, specific inhibitor of farnesyl protein transferase. This transferase is necessary for activation of ras proteins that when mutated are frequently found in human cancers. SCH 66336 thus represents a new class of antineoplastic compounds. It was developed by Schering Plough and has not yet been tested in humans. METHODS: Patients eligible for this phase I trial will be those with histologically confirmed solid tumor malignancies, without bone marrow involvement, for which no conventional therapies are available. No more than two prior chemotherapy regimens for advanced disease are permitted. At each dose level, subjects will receive a single-dose of SC 66336 followed by a 24 hour observation period (cycle l only). Subjects will then receive SC 66336 twice daily for 13 consecutive days. At each dose level, pharmacokinetic evaluations will be performed on day 1 and day 14. Patients will be housed on the Clinical Research Unit for monitoring and pharmacokinetics for their first dose and repeat pharmacokinetics on day 14. One patient each will be treated at each dose level until DLT is observed. If grade II toxicity (non-DLT) is observed during the first 28 days, an additional 2 subjects will be enrolled at that dose level. If one of three patients has non-DLT, then escalation will continue with one patient at each dose level. If 2 or 3 subjects have non-DLT, the dose escalation schedule will be changed to 3 subjects at each dose level. Patients may continue to take SC 66336 in the absence of disease progression (28-day cycles).