COLOVERT – Conversion therapy in colorectal cancer with peritoneal metastases not amenable to upfront cytoreductive surgery and HIPEC: a phase II “pick-the-winner” open-label randomized trial

Prior treatment

• Previous severe toxicity/allergic reactions to the systemic chemotherapy agents included in this study • Unable to tolerate full dose systemic chemotherapy treatment due to comorbidity or previous remaining toxicity (e.g. neurotoxicity) or DPYD deficiency • Deficient mismatch repair cancers are excluded • Previous CRS or HIPEC or other large open abdominal surgery leading to significant intraperitoneal adhesions. (laparoscopic procedures are ok) • Previous severe abdominal septicemia or other causes that may significantly increase the risk of intraperitoneal adhesions (a staging laparoscopy may be allowed to determine this) • Pregnant or lactating (nursing) women • Active infections requiring antibiotics • Active liver disease with positive serology for active hepatitis B, C, or known HIV • Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to and up to 4 weeks after study treatment • Lower and intermediate rectal cancers are excluded (above >10cm accepted) • Indication for preoperative radiation

• Provision of written informed consent prior to any study specific procedures. • ECOG Performance Status Score 0,1 or 2 alternatively Karnofsky 60-100 • Adequate kidney, liver, bone marrow function according to laboratory tests • For females of childbearing potential, a negative pregnancy test must be documented. • ≥ 18 years old and <80 years old • Colorectal cancer (>10cm from anal verge) with CT assessable synchronous or metachronous peritoneal metastases +/- primary tumor • CT-PCI > 10 (which translates often to surgical PCI >15) as judged at the HIPEC multidisciplinary board meeting but considered candidate for CRS/HIPEC in the case of significant tumor response. • CT-PCI < 10 allowed if conversion therapy is necessary to be eligible for CRS+/-HIPEC • RAS mutations and wild-type cancers can both be included. • No previous treatment for peritoneal metastatic disease