Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stomach CAncer: a Feasibility Study

Study Overview
=================
Brief Summary
-----------------
Rationale: For patients with peritoneal metastases of gastric origin, there is no consensus on the optimal treatment strategy. Several Asian and Western studies demonstrated hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CS) to result in a prolonged survival compared to palliative systemic treatment. Morbidity and mortality rates of HIPEC and CS appear to be acceptable. In the Netherlands, this treatment is not yet introduced, therefore patients with peritoneal metastases of gastric origin are precluded from surgery and will be treated with palliative chemotherapy or best support of care. Objective: To assess the safety and feasibility of HIPEC and CS in Western patients with peritoneal metastases of gastric cancer, in terms of morbidity and mortality. Secondary objective is to determine the effect on survival and recurrence. Study design: Mono centre prospective phase II single-arm feasibility study. Study population: Western patients diagnosed with resectable (cT1-4b, N1-3) gastric cancer with clinical or pathologically proven peritoneal metastases without distant metastases. Intervention: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CS) with Cisplatin. Main study parameters/endpoints: Primary outcome is the safety and feasibility of the intervention, measured by the percentage of overall surgical complications grade ≥3 as stated by the Common Terminology Criteria for Adverse Events. Secondary outcomes are intraoperative events, postoperative morbidity and mortality, postoperative recovery, including quality of life, and disease free- and overall survival. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The additional burden for the patient mainly consists of HIPEC and CS.Furthermore, patients will undergo additional staging in order to exclude unresectable disease, and neoadjuvant chemotherapy regimen (3 drugs) instead of a palliative chemotherapy regimen (2 drugs). Postoperative care and outpatient visits are performed according to current protocols on HIPEC and CS for colon cancer and nation-wide protocols on gastric cancer surgery. The study is associated with a high risk classification. As there is a potential survival benefit, a small chance for curation and possibly a higher quality of life, we consider the additional burden and risks justified. This study is designed as a one group study, which eliminates group relatedness.

Official Title
-----------------
Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stomach CAncer: a Feasibility Study

Conditions
-----------------
Gastric Cancer, Peritoneal Carcinomatosis, HIPEC

Intervention / Treatment
-----------------
* Drug: Perioperative chemotherapy
* Procedure: Cytoreduction
* Drug: HIPEC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven adenocarcinoma of the stomach. Surgical resectable carcinoma (T1-4b, N1-3) (table 1) Pathological proven peritoneal metastases Peritoneal Cancer Index (PCI) ≤12 WHO performance status 0,1 or 2 and ASA 1-3 Age ≥ 18 Written informed consent Exclusion Criteria: Distant metastases other than peritoneal metastases Siewert type I/II gastro-esophageal junction tumor 22. Peritoneal carcinomatosis as a presentation of recurrent disease Pregnancy Any contraindication to cisplatin, e.g. Hypersensitivity HIV infection inadequate bone marrow function (ANC <1.5x109/L or Platelets <100x109/L) inadequate hepatic function (>1.5 x ULN, ALAT and ASAT >2.5 x ULN) inadequate renal function (Creatinine clearance <50 ml/min)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study population<br> | Drug: Perioperative chemotherapy<br>* Perioperative chemotherapy<br>Procedure: Cytoreduction<br>* Cytoreductive surgery<br>Drug: HIPEC<br>* Hyperthermic intraperitoneal chemotherapy (HIPEC) with 100mg/m2 cisplatin<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 3 | From the day of surgery to hospital discharge or 30 days postoperative, whichever is last | 
| Mortality | Postoperative mortality | From the day of surgery to 30 days postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Overall and disease free survival | Up to 5 years postoperative | 
| Recovery | ICU stay, hospital stay | From the day of surgery to hospital discharge or 30 days postoperative, whichever is last | 
| Quality of Life | EORTC-QLQ-C30 and EORTC-QLQ-STO22 | Up to 5 years postoperative | 
| Readmissions | Readmissions after hospital discharge | Up to 30 days after hospital discharge |