Gastrectomy + Cytoreductive Surgery + HIPEC for Gastric Cancer With Peritoneal Dissemination.

A randomized controlled two-armed phase III trial for gastric cancer patients with peritoneal dissemination. Randomization between gastrectomy + cytoreductive surgery + HIPEC (experimental arm) and palliative systemic chemotherapy (standard arm).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Age ≥ 18 years
* Biopsy proven primary adenocarcinoma (or undifferentiated carcinoma) of the stomach. Including tumours at the oesophagogastric junction provided that the bulk of the tumour is located in the stomach, and, the intended surgical treatment is a gastric resection and not an oesophagectomy. A high intra-thoracic anastomosis is allowed, but not if a thoracotomy is necessary.
* cT3-cT4 tumour (TNM classification, 7th edition), considered to be resectable (including lymph nodes)
* Limited peritoneal carcinomatosis (PCI \<7) and/ or tumour positive peritoneal cytology confirmed by laparoscopy or laparotomy and proven by pathological examination
* Treatment with systemic chemotherapy, with the latest course ending within 8 weeks prior to inclusion. All currently standard chemotherapy regimens are acceptable
* Absence of disease progression during systemic chemotherapy (prior to inclusion)
* WHO performance status 0-2
* Adequate bone marrow, hepatic and renal function. Minimally acceptable laboratory values at start of the study inclusion:

  * ANC ≥ 1.5 x 109 /L
  * Platelet count ≥ 100 x 109 /L
  * Serum bilirubin ≤ 1.5 x ULN, and ALAT and ASAT ≤ 2.5 x ULN
  * Creatinine clearance ≥ 50 ml/min (measured or calculated by Cockcroft-Gault formula)
* For female patients who are not sterilised or in menopause (i.e., amenorrhea ≥1 year if age ≥60 years, or ≥2 years if age \<60 years):

  * negative pregnancy test (urine/serum)
  * no breast feeding or active pregnancy ambition
  * reliable contraceptive methods
* Signed informed consent

Exclusion Criteria:

* Distant metastases (e.g., liver, lung, para-aortic lymph nodes; i.e., stations 14 and 16) or small bowel dissemination
* Recurrent gastric cancer
* Prior resection of the primary gastric tumour
* Non-synchronous peritoneal carcinomatosis
* Current other malignancy (other than cervix carcinoma and basalioma)
* Uncontrolled infectious disease or known infection with Human Immunodeficiency Virus type -1 or -2
* A known history of hepatitis B or C with active viral replication
* Recent myocardial infarction (\< 6 months) or unstable angina
* Any medical condition not yet specified above that is considered to interfere with study procedures, including adequate follow-up and compliance and/or would jeopardise safe treatment
* Known hypersensitivity for any of the applied chemotherapeutic agents and/or their solvents

• BACKGROUNDvan der Kaaij RT, Braam HJ, Boot H, Los M, Cats A, Grootscholten C, Schellens JH, Aalbers AG, Huitema AD, Knibbe CA, Boerma D, Wiezer MJ, van Ramshorst B, van Sandick JW. Treatment of Peritoneal Dissemination in Stomach Cancer Patients With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Rationale and Design of the PERISCOPE Study. JMIR Res Protoc. 2017 Jul 13;6(7):e136. doi: 10.2196/resprot.7790. PMID 28705789
• DERIVEDQuik JSE, Vollebergh MA, Retel VP, van der Sluis K, Koemans WJ, van der Kaaij RT, Voets MM, Luyer MDP, van Hellemond IEG, Wijnhoven BPL, Mostert B, van Hillegersberg R, Mohammad NH, van Etten B, de Groot DJ, Helminen O, Hedberg J, Cashin PH, Harbjerg JL, Veenhof AAFA, Hartemink KJ, Kodach LL, van der Noort V, van Sandick JW; PERISCOPE II consortium. Systemic therapy, gastrectomy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy versus systemic therapy alone for gastric cancer with limited peritoneal metastases (PERISCOPE II): final results of a multicentre, randomised, controlled, phase 3 trial after an unplanned commissioned interim analysis. Lancet Oncol. 2026 Aug;27(8):1031-1042. doi: 10.1016/S1470-2045(26)00144-0. Epub 2026 Jul 8. PMID 42419336
• DERIVEDRijken A, Pape M, Simkens GA, de Hingh IHJT, Luyer MDP, van Sandick JW, van Laarhoven HWM, Verhoeven RHA, van Erning FN. Peritoneal metastases from gastric cancer in a nationwide cohort: Incidence, treatment and survival. Int J Cancer. 2024 Mar 15;154(6):992-1002. doi: 10.1002/ijc.34780. Epub 2023 Nov 2. PMID 37916797
• DERIVEDKoemans WJ, van der Kaaij RT, Boot H, Buffart T, Veenhof AAFA, Hartemink KJ, Grootscholten C, Snaebjornsson P, Retel VP, van Tinteren H, Vanhoutvin S, van der Noort V, Houwink A, Hahn C, Huitema ADR, Lahaye M, Los M, van den Barselaar P, Imhof O, Aalbers A, van Dam GM, van Etten B, Wijnhoven BPL, Luyer MDP, Boerma D, van Sandick JW. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II). BMC Cancer. 2019 May 6;19(1):420. doi: 10.1186/s12885-019-5640-2. PMID 31060544