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

Sponsor

The Netherlands Cancer Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03348150

Collaborator

Erasmus Medical Center (Other), UMC Utrecht (Other), University Medical Center Groningen (Other), Catharina Ziekenhuis Eindhoven (Other)

182

Enrollment

Location

Arms

144

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasm Peritoneal Carcinomatosis	Procedure: Cytoreductive surgery + Gastrecomy Drug: Hyperthermic Intraperitoneal Chemotherapy (HIPEC)	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

182 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 randomization1:1 randomization

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Treatment of Peritoneal Dissemination in Stomach Cancer Patients With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Actual Study Start Date :

Oct 1, 2017

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gastrecomy + Cytoreductive surgery + HIPEC	Procedure: Cytoreductive surgery + Gastrecomy Complete cytoreduction followed by a (sub)total gastric resection with D2 lymphadenectomy. Drug: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) HIPEC: perfusion with oxaliplatin (460mg/m2 ) (42 °C) followed by docetaxel (50mg/m2 ) (37°C)
No Intervention: palliative systemic chemotherapy

Arm

Intervention/Treatment

Experimental: Gastrecomy + Cytoreductive surgery + HIPEC

Procedure: Cytoreductive surgery + Gastrecomy

Complete cytoreduction followed by a (sub)total gastric resection with D2 lymphadenectomy.

Drug: Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

HIPEC: perfusion with oxaliplatin (460mg/m2 ) (42 °C) followed by docetaxel (50mg/m2 ) (37°C)

No Intervention: palliative systemic chemotherapy

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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