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

Phase 3

Recruiting

• Conditions: Peritoneal Carcinomatosis; Stomach Neoplasm
• Interventions: Procedure: Cytoreductive surgery + Gastrecomy; Drug: Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

• Registration Number: NCT03348150
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

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).

Detailed Description

Rationale: For gastric cancer patients with peritoneal carcinomatosis palliative systemic chemotherapy is the standard treatment in the Netherlands. There are no potentially curative treatment options. Peritoneal carcinomatosis, in contrast to lymphatic and haematogenous dissemination, should be regarded as locoregional extension of disease. Administering chemotherapeutic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations of cytotoxic drugs can be delivered directly into the peritoneal cavity with little systemic toxicity. The combination of intraperitoneally administered chemotherapy with cytoreductive surgery and a radical gastrectomy has shown promising results in gastric cancer patients in Asia. As with other gastric cancer issues, the results obtained in Asian patients cannot be extrapolated directly to Western patients.

Objective: The primary aim of this study is to compare the overall survival between gastric cancer patients with limited peritoneal carcinomatosis and/ or tumour positive peritoneal cytology treated with gastrectomy, cytoreductive surgery and HIPEC and those treated with the current standard treatment, i.e. palliative systemic chemotherapy.

Study design : This is a multicentre randomised controlled two-armed phase III trial. Patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy combined with cytoreductive surgery and HIPEC (experimental treatment).

Study population: Gastric cancer patients are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal carcinomatosis (\<7) and/ or tumour positive cytology is confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy (prior to inclusion) was without disease progression.

Main study parameters/endpoints: The study sample size (182 patients) is calculated from the hypothesis that the median overall survival of the patients treated according to protocol in the experimental arm is 18 months, as compared to a median overall survival of 10 months in the standard arm. Statistical analysis will be done according to the intention-to-treat principle.

Study Timeline

• Study Start: 2017-10-01
• Study First Submitted: 2017-11-15
• Study First Submitted QC: 2017-11-15
• Study First Posted: 2017-11-20
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-13
• Last Update Posted: 2023-12-20
• Primary Completion: 2026-10-01
• Study Completion: 2029-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 182

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gastrecomy + Cytoreductive surgery + HIPEC	Cytoreductive surgery + Gastrecomy	Gastrectomy combined with cytoreductive surgery and HIPEC (experimental treatment)
Gastrecomy + Cytoreductive surgery + HIPEC	Hyperthermic Intraperitoneal Chemotherapy (HIPEC)	Gastrectomy combined with cytoreductive surgery and HIPEC (experimental treatment)

Primary Outcome Measures

Name	Time	Method
overall survival	5 years	To compare the overall survival between gastric cancer patients with limited peritoneal carcinomatosis and/ or tumour positive peritoneal cytology treated with gastrectomy, cytoreductive surgery and HIPEC and those treated with the current standard treatment, i.e. palliative systemic chemotherapy.

Secondary Outcome Measures

Name	Time	Method
progression free survival	5 years	To compare the progression free survival between gastric cancer patients with limited peritoneal carcinomatosis and/ or tumour positive peritoneal cytology treated with gastrectomy, cytoreductive surgery and HIPEC and those treated with the current standard treatment, i.e. palliative systemic chemotherapy.
costs and health benefits	5 years	To compare the costs and health benefits of a gastrectomy in combination with cytoreductive surgery and HIPEC, to the costs and health benefits of standard palliative systemic chemotherapy in patients with limited peritoneal carcinomatosis and/ or tumour positive peritoneal cytology.
treatment-related toxicity	5 years	To study treatment-related toxicity in gastric cancer patients with limited peritoneal carcinomatosis and/ or tumour positive peritoneal cytology treated with gastrectomy, cytoreductive surgery and HIPEC.

Trial Locations

Locations (1)

Antoni van Leeuwenhoek/ Netherlands Cancer institute; 🇳🇱 Amsterdam, Netherlands