Department of Surgical Oncology, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands.
Department of Surgical Oncology, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands
BMJ Open. 2022 Jun 22;12(6):e062907. doi: 10.1136/bmjopen-2022-062907.
Malignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.
The INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.
The Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.
NL9718. EudraCT: 2021-003637-11.
恶性腹膜间皮瘤（MPM）是一种罕见的、侵袭性肿瘤，主要来源于腹膜。唯一潜在的治愈性治疗方法是细胞减灭术（CRS）联合腹腔内热灌注化疗（HIPEC）。然而，大多数患者不符合该治疗方法的条件。这些患者接受全身治疗的获益有限，但其代价是相当大的发病率。因此，需要为 MPM 患者提供适当的姑息治疗选择。由于 MPM 很少在腹腔外扩散，这些患者可能受益于局部治疗。更高、更有效的化疗剂量可以直接在疾病部位给予。全身吸收将受到限制，可能导致毒性降低。INTERACT MESO 试验的目的是确定 MPM 患者腹腔内紫杉醇单药治疗的最大耐受剂量。次要终点是评估该治疗的安全性和毒性、可行性和药代动力学特征。
INTERACT MESO 试验是一项前瞻性、开放标签、单中心、I 期研究，采用经典的三加三剂量递增设计。研究人群包括患有原发性 MPM、无腹腔外疾病且不符合 CRS-HIPEC 条件的成年患者。根据 CRS-HIPEC 的标准护理评估，患者将接受诊断性腹腔镜检查以确定 CRS-HIPEC 的可行性。如果认为 CRS-HIPEC 不可行，则会放置腹膜端口导管（PAC）系统。通过这个 PAC，将给予 8-16 个每周的腹腔内化疗周期。
中央人体研究伦理委员会（CCMO，荷兰海牙）和医学研究伦理委员会（METC，荷兰鹿特丹）已批准执行本研究方案。该试验的结果将提交给同行评议的科学期刊发表。
NL9718。EudraCT：2021-003637-11。
