CLINICAL TRIAL: STUDY OF CAPECITABINE, OXALIPLATIN AND BEVACIZUMAB FOR METASTATI

临床试验：卡培他滨、奥沙利铂和贝伐单抗治疗转移的研究

• 批准号: 7717911
• 负责人: GEORGE E FISHER
• 金额: $ 1.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717911
• 关键词: Benefits and Risks; Bevacizumab/Capecitabine; Bevacizumab/Capecitabine/Oxaliplatin; Biochemical Markers; Cancer Patient; Capecitabine/Oxaliplatin; Clinical; Clinical Trials; Colorectal Cancer; Computer Retrieval of Information on Scientific Projects Database; Daily; Disease; Disease Progression; Dose; Effectiveness; Enrollment; Fluorouracil; Fluorouracil/Leucovorin Calcium/Oxaliplatin; Funding; Grant; Image; Institution; Laboratories; Location; Neuroendocrine Tumors; Oral cavity; Patients; Phase; Phase II Clinical Trials; Progressive Disease; Rate; Relative (related person); Research; Research Personnel; Resources; Safety; Schedule; Source; Surrogate Endpoint; Symptoms; Time; Toxic effect; Treatment Protocols; United States National Institutes of Health; Upper arm; Week; X-Ray Computed Tomography; bevacizumab; capecitabine; concept; day; design; experience; metastatic colorectal; neurotoxicity; oxaliplatin; response; trend; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. STUDY RATIONALE Given the lack of other viable treatment options for metastatic neuroendocrine tumors, contrasted with our positive anecdotal experience, and the relative tolerability of the treatment regimen for colorectal cancer patients, we propose a single-institution phase II trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors. STUDY DESIGN This will be a single-institution, phase II single-arm study. All patients enrolled will receive the experimental treatment regimen. DESCRIPTION OF THE STUDY All enrolled patients will receive bevacizumab 7.5 mg/kg intravenously followed by oxaliplatin 130 mg/m2 intravenously on day 1 of a 21 day cycle. Patients will receive capecitabine 1000 mg/m2 twice daily by mouth on days 1-14, followed by a one week break. Computed tomography (CT) imaging will be done at baseline and every 3 cycles to assess for response or progression. After 12 weeks (4 cycles) on study, patients will discontinue oxaliplatin and only receive capecitabine and bevacizumab according to the above schedule until disease progression or unacceptable toxicity. Patients will be assessed by clinical and laboratory exam at least once per cycle (more frequently as needed) and dose reductions will be allowed for unacceptable toxicity. Patients will be assessed for response by CT imaging once every 4 cycles, or until symptoms suggestive of progressive disease arise. RATIONALE FOR STUDY DESIGN Capecitabine, oxaliplatin, and bevacizumab (XELOX+A) is a well-established regimen for metastatic colorectal cancer in the schedule described above. However, the cumulative neurotoxicity of oxaliplatin often limits its continued use, despite its effectiveness in producing a treatment response. For metastatic colorectal cancer, a new schedule of FOLFOX (a predecessor regimen of XELOX using infusional fluorouracil instead of capecitabine) called the OPTIMOX regimen incorporates intermittent breaks from oxaliplatin (25). With reintroduction of oxaliplatin after a twelve week break, the OPTIMOX investigators found no significant difference in major efficacy parameters, but a trend towards decreased toxicity with the intermittent schedule. Given that patients with metastatic neuroendocrine tumors are not uniformly demonstrating rapid progression, the risk-benefit ratio of continuous oxaliplatin and increased neurotoxicity favors the OPTIMOX concept. Therefore, we have incorporated a discontinuation of oxaliplatin after 4 cycles, with reintroduction of oxaliplatin upon evidence of disease progression by RECIST criteria. During the hiatus from oxaliplatin, patients will continue on capecitabine and bevacizumab, both of which have far more acceptable safety profiles for patients with disease that has the potential for long-term stability. OBJECTIVES: PRIMARY 1.Determine an estimation of median time to progression (TTP) for patients treated with bevacizumab in combination with capecitabine and oxaliplatin 2.Assess the toxicities associated with this regimen SECONDARY 1.Determine objective response rate (RR) for patients treated with this regimen 2.Conduct exploratory analyses of efficacy according to degree of tumor differentiation and primary location 3.Determine utility of biochemical markers as a surrogate endpoint for tumor response

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 研究原理 鉴于转移性神经内分泌肿瘤缺乏其他可行的治疗方案，与我们的积极轶事经验相比，以及结直肠癌患者治疗方案的相对耐受性，我们提出一项单机构 II 期试验，研究卡培他滨、奥沙利铂和贝伐单抗对转移性神经内分泌肿瘤患者的疗效。 研究设计 这将是一项单机构、II 期单组研究。 所有入组的患者都将接受实验治疗方案。 研究描述 所有入组患者将接受贝伐单抗 7.5 mg/kg 静脉注射，随后在 21 天周期的第一天静脉注射奥沙利铂 130 mg/m2。 患者将在第 1-14 天每天两次口服卡培他滨 1000 mg/m2，然后休息一周。将在基线和每 3 个周期进行计算机断层扫描 (CT) 成像，以评估反应或进展。 研究12周（4个周期）后，患者将停止奥沙利铂治疗，仅根据上述时间表接受卡培他滨和贝伐单抗治疗，直至疾病进展或出现不可接受的毒性。 每个周期至少对患者进行一次临床和实验室检查（根据需要更频繁），并且如果出现不可接受的毒性，则允许减少剂量。 每 4 个周期一次通过 CT 成像评估患者的反应，或直至出现提示疾病进展的症状。 研究设计的基本原理 卡培他滨、奥沙利铂和贝伐单抗 (XELOX+A) 是上述方案中针对转移性结直肠癌的成熟治疗方案。 然而，尽管奥沙利铂能有效产生治疗反应，但其累积的神经毒性往往限制其继续使用。 对于转移性结直肠癌，新的 FOLFOX 方案（XELOX 的前身方案，使用输注氟尿嘧啶代替卡培他滨）称为 OPTIMOX 方案，其中包括间歇性停用奥沙利铂 (25)。 停药 12 周后重新引入奥沙利铂，OPTIMOX 研究人员发现主要疗效参数没有显着差异，但间歇性方案有毒性降低的趋势。 鉴于转移性神经内分泌肿瘤患者并未一致表现出快速进展，持续奥沙利铂和增加的神经毒性的风险效益比有利于 OPTIMOX 概念。 因此，我们在 4 个周期后停用奥沙利铂，并在根据 RECIST 标准出现疾病进展证据后重新引入奥沙利铂。 在奥沙利铂停用期间，患者将继续服用卡培他滨和贝伐珠单抗，这两种药物对于患有有可能长期稳定的疾病的患者来说具有更可接受的安全性。 目标： 基本的 1.确定接受贝伐单抗联合卡培他滨和奥沙利铂治疗的患者的中位疾病进展时间 (TTP) 的估计 2.评估与该方案相关的毒性 中学 1.确定接受该方案治疗的患者的客观缓解率（RR） 2.根据肿瘤分化程度和原发部位进行疗效探索性分析 3.确定生化标志物作为肿瘤反应替代终点的效用