Neoadjuvant intraperitoneal chemotherapy (irinotecan) combined with systemic therapy (mFOLFOX4 and bevacizumab) prior to cytoreductive surgery and HIPEC for patients with isolated resectable colorectal peritoneal metastases: protocol of a phase II, m

The peritoneum is one of the most common metastatic sites in patients with colorectal cancer. In patients with limited peritoneal metastases, the only option with curative intent is cytoreductive surgery, often combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Although CRS-HIPEC offers long-term survival and even curation for a subset of patients, recurrence in the peritoneal cavity is common. It can be argued that the single administration of heated intraperitoneal chemotherapy might not be sufficient to radically eradicate the remaining microscopic intraperitoneal cancer cells after CRS. Due to the presence of the plasma-peritoneal barrier, chemotherapy concentrations in the peritoneal cavity are low after systemic administration. Adding intraperitoneal chemotherapy offers a solution to provide repetitive and local exposure of chemotherapy. The primary endpoint of the current phase II trial is the feasibility of combined intraperitoneal (irinotecan) and systemic therapy (mFOLFOX4-bevacizumab) prior to CRS-HIPEC in patients with resectable colorectal peritoneal metastases. Secondary endpoints are histopathological and radiological treatment response, safety of the treatment, the potential value of PET-CT in treatment response monitoring, quality of life, and disease-free survival, which is assessed until six months after CRS-HIPEC. INTERACT-PLUS is a phase II, single-arm trial conducted in four expert centers for the treatment of patients with colorectal peritoneal metastases. The study population comprises 40 patients with limited, macroscopic peritoneal metastases. Patients undergo a diagnostic laparoscopy to evaluate the peritoneal cancer index (PCI). In case of a PCI between 1 and 20, a peritoneal access port for intraperitoneal administration of irinotecan is placed subcutaneously. Simultaneously with intraperitoneal irinotecan, patients receive intravenous 5-fluorouracil/leucovorin with oxaliplatin (mFOLFOX4) and bevacizumab. Depending on response and tolerability, patients receive a maximum of six cycles, the last two without bevacizumab, prior to CRS-HIPEC. This study is done in accordance with the Helsinki declaration and Good Clinical Practice requirements. All patients will provide written informed consent. This clinical trial is approved by the research medical ethics committee (Rotterdam, the Netherlands), by the Clinical Trials Information System, and by the institutional boards of all participating research centers. Results will be presented to medical professionals and patients as well as submitted for publication in peer-reviewed medical journals. 2024-512318-16-00.