Intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus systemic chemotherapy alone: a randomized controlled trial [AIO-PAK-0219 METAPANC]

局部可手术但寡转移性胰腺癌患者的强化治疗——多模式手术治疗与单纯全身化疗的比较：一项随机对照试验[AIO-PAK-0219 METAPANC]

• 批准号: 437570515
• 负责人: Professor Dr. B. Michael Ghadimi
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/437570515?language=en
• 关键词: Intensified; treatment; patients; local; operable

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer entity and initially presents in more than 60% of the patients with metastasis. In the last years systemic therapy with the FOLFIRINOX protocol (Oxaliplatin, Irinotecan, 5-FU) has demonstrated as an effective therapy with increased survival and response rates above 30 % with tumor regression up to complete responses. However, recurrence of disease or secondary resistance inevitably occur leading to an overall survival of only approximately 11 months. In the group of metastasized PDACs a subgroup of patients presents with oligometastasized disease with a maximum of three liver metastases in a synchronous or metachronous fashion, though there is no consensus definition. As in other gastrointestinal cancers there might exist a potential curative window of opportunity for such patients including surgery. Thus, while continued chemotherapy usually in a de-escalated fashion due to toxicity of FOLFIRINOX is the standard of care, surgical resection of the primary cancer and the metastases may be offered to patients. However, the relevance of surgery in oligometastasized patients is unclear up to now and many patients in such context are treated individually in Europe. There exist neither prospective data nor data from controlled randomized clinical trials worldwide. In the applied prospective randomized phase-III trial (METAPANC) the relevance of surgical resection of the primary cancer and the metastases after induction chemotherapy with FOLFIRINOX will be investigated. Only patients with tumor regression or stable disease after at least 4 months of chemotherapy will be included. Only patients in whom a curative and complete resection of the primary and the metastases can be achieved (experimental arm) will be randomized. The standard arm consists of a 4-months chemotherapy (FOLFIRINOX) followed by a de-escalating chemotherapy (standard of care). The primary endpoint is overall survival. This prospective randomized trial is accompanied by a translational research program including the central sampling and molecular characterization of tumor tissue, liquid biopsy and radiomics approaches. Despite the increasing incidence of PDAC the number of oligometastatic patients eligible for this trial is small and defines it as ”rare disease“. Therefore, the largest German Hospitals (AIO/ACO Studie) and the Dutch Pancreatic Cancer Group (DPCG) as well as a two northern European centers (Oslo/NOR and Helsinki/FIN) will recruit patients in this trial. The study groups in the three countries have expressed their strong interest for this trial. We envision practice-changing results upon successful completion of the phase III trial with respect to the inclusion of surgical resection in multimodal regimens for selected patients with oligometastatic PDAC.

胰腺导管腺癌（PDAC）是最具侵袭性的癌症实体，最初出现在超过60%的转移患者中。在过去几年中，FOLFIRINOX方案（奥沙利铂、伊立替康、5-FU）的全身治疗已被证明是一种有效的治疗方法，生存率和缓解率均高于30%，肿瘤消退至完全缓解。然而，疾病复发或继发性耐药性不可避免地发生，导致总生存期仅约11个月。在转移性PDAC组中，一个患者亚组表现为寡转移性疾病，最多同时或异时发生3处肝转移，但尚无一致定义。与其他胃肠道癌症一样，这类患者可能存在潜在的治疗机会，包括手术。因此，虽然由于FOLFIRINOX的毒性而通常以降级方式继续化疗是治疗标准，但可以向患者提供原发性癌症和转移瘤的手术切除。然而，到目前为止，手术在寡转移患者中的相关性尚不清楚，在欧洲，这种情况下的许多患者都是单独治疗的。既没有前瞻性数据，也没有来自全球对照随机临床试验的数据。在应用的前瞻性随机III期试验（METAPANC）中，将研究FOLFIRINOX诱导化疗后原发癌和转移癌手术切除的相关性。仅纳入化疗至少4个月后肿瘤消退或疾病稳定的患者。仅对能够实现原发灶和转移灶根治性和完全切除的患者（实验组）进行随机化。标准组包括4个月化疗（FOLFIRINOX），随后是递减化疗（标准治疗）。主要终点是总生存期。这项前瞻性随机试验伴随着一项转化研究计划，包括肿瘤组织的中心取样和分子表征、液体活检和放射组学方法。尽管PDAC的发病率不断增加，但符合本试验条件的寡转移患者数量较少，并将其定义为“罕见疾病”。因此，最大的德国医院（AIO/ACO Studie）和荷兰胰腺癌研究组（DPCG）以及两个北方欧洲中心（奥斯陆/NOR和赫尔辛基/FIN）将在本试验中招募患者。这三个国家的研究小组对这项试验表示了浓厚的兴趣。我们设想在成功完成III期试验后，在选定的寡转移性PDAC患者的多模式治疗方案中纳入手术切除，将改变实践结果。