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Abstract：
BACKGROUND: Cytotoxic chemotherapy combinations and targeted agents represent established treatment concepts in advanced pancreatic neuroendocrine tumors (PNETs). However, response rates, side effects and outcome data strongly vary among these therapeutic approaches. Head-to-head comparisons between chemo- and molecular therapies are missing and secondary resistances frequently occur. The RamuNET trial aims to identify the effectiveness of dual treatment with DTIC and ramucirumab in progressive advanced PNET patients.
METHODS: The RamuNET study is an investigator-initiated multicenter prospective single-arm trial to evaluate the efficacy of ramucirumab in combination with dacarbazine (DTIC) over a period of at least 6 months. Patients with progressive well-differentiated and metastatic pancreatic neuroendocrine tumors are eligible. The study aims to include 45 patients over a period of 24 months with a minimum follow-up of 24 months. The primary endpoint is disease control after 6 months. Secondary endpoints include progression-free survival, biochemical response, overall survival, quality of life and toxicity. Based on the hypothesis that 80% of the patients can achieve a disease control after 6 months, the sample size calculation follows an exact binomial single-stage design. H0: p < =p0 = 60% versus H1: p > =p1 = 80%, alpha = 0.05, beta = 0.1.
CONCLUSIONS: This study investigates a new therapeutic approach using the combination of cytotoxic and targeted antiangiogenic therapy in advanced PNET. If positive, this trial will be the basis for a randomized two-arm study to investigate the combination of ramucirumab and DTIC against other established therapies in PNET.
BACKGROUND: EudraCT: 2017-001207-68 . Date of registration: 2018.01.03.
METHODS: The RamuNET study is an investigator-initiated multicenter prospective single-arm trial to evaluate the efficacy of ramucirumab in combination with dacarbazine (DTIC) over a period of at least 6 months. Patients with progressive well-differentiated and metastatic pancreatic neuroendocrine tumors are eligible. The study aims to include 45 patients over a period of 24 months with a minimum follow-up of 24 months. The primary endpoint is disease control after 6 months. Secondary endpoints include progression-free survival, biochemical response, overall survival, quality of life and toxicity. Based on the hypothesis that 80% of the patients can achieve a disease control after 6 months, the sample size calculation follows an exact binomial single-stage design. H0: p < =p0 = 60% versus H1: p > =p1 = 80%, alpha = 0.05, beta = 0.1.
CONCLUSIONS: This study investigates a new therapeutic approach using the combination of cytotoxic and targeted antiangiogenic therapy in advanced PNET. If positive, this trial will be the basis for a randomized two-arm study to investigate the combination of ramucirumab and DTIC against other established therapies in PNET.
BACKGROUND: EudraCT: 2017-001207-68 . Date of registration: 2018.01.03.
摘要：
背景：细胞毒性化疗组合和靶向药物代表了晚期胰腺神经内分泌肿瘤（PNETs）的既定治疗理念。然而,反应率，这些治疗方法的副作用和结果数据差异很大。缺少化学疗法和分子疗法之间的头对头比较，并且经常发生继发性耐药性。RamuNET试验旨在确定DTIC和雷莫西单抗双重治疗在进展性晚期PNET患者中的有效性。
方法：RamuNET研究是一项由研究者发起的多中心前瞻性单臂试验，用于评估雷莫西单抗联合达卡巴嗪（DTIC）在至少6个月的时间内的疗效。患有进行性高分化和转移性胰腺神经内分泌肿瘤的患者是合格的。该研究旨在包括45名患者，为期24个月，最少随访24个月。主要终点是6个月后的疾病控制。次要终点包括无进展生存期，生化反应，总生存率,生活质量和毒性。基于假设80％的患者可以在6个月后实现疾病控制，样本量计算遵循精确的二项式单级设计。H0:p<=p0=60%与H1:p>=p1=80%,α=0.05,β=0.1。
结论：本研究探讨了在晚期PNET中使用细胞毒性和靶向抗血管生成疗法的联合治疗方法。如果是积极的，这项试验将成为一项随机双臂研究的基础,该研究旨在研究雷莫西单抗和DTIC联合治疗对PNET中其他既定治疗的效果.
背景：EudraCT：2017-001207-68。注册日期：2018.01.03。
方法：RamuNET研究是一项由研究者发起的多中心前瞻性单臂试验，用于评估雷莫西单抗联合达卡巴嗪（DTIC）在至少6个月的时间内的疗效。患有进行性高分化和转移性胰腺神经内分泌肿瘤的患者是合格的。该研究旨在包括45名患者，为期24个月，最少随访24个月。主要终点是6个月后的疾病控制。次要终点包括无进展生存期，生化反应，总生存率,生活质量和毒性。基于假设80％的患者可以在6个月后实现疾病控制，样本量计算遵循精确的二项式单级设计。H0:p<=p0=60%与H1:p>=p1=80%,α=0.05,β=0.1。
结论：本研究探讨了在晚期PNET中使用细胞毒性和靶向抗血管生成疗法的联合治疗方法。如果是积极的，这项试验将成为一项随机双臂研究的基础,该研究旨在研究雷莫西单抗和DTIC联合治疗对PNET中其他既定治疗的效果.
背景：EudraCT：2017-001207-68。注册日期：2018.01.03。
