Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in Gastro- Intestinal Cancer

Study Overview
=================
Brief Summary
-----------------
Patients with gastric or colon cancer with peritoneal carcinomatosis will receive a biopsy of the tumor during their primary curative surgery. The operation is performed according to standard and includes resection of the primary tumor and any metastases and followed by HIPEC (Intraperitoneal hyperthermic chemoperfusion) according to the respective hospital standard. Organoid cultures from the biopsies are established in the research laboratory. Various chemotherapeutic agents are tested on these tumor organoids in the laboratory and the tumor organoids are analyzed in detail with regard to genetic alterations in order to find alterations that can be addressed, if necessary, by means of targeted drugs against peritoneal carcinomatosis.

Official Title
-----------------
Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in Gastro- Intestinal Cancer

Conditions
-----------------
Gastric Cancer, Colon Cancer, Peritoneal Carcinomatosis

Intervention / Treatment
-----------------
* Other: Establishment of organoid cultures and in vitro sensitivity testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: (Suspected) synchronous or metachronous peritoneal metastasis of adenocarcinoma of the stomach / gastroesophageal junction (GEJ) or of the colon or rectum intraoperative histological confirmation of synchronous or metachronous peritoneal carcinomatosis in gastric carcinoma (incl. GEJ) or colon carcinoma (incl. rectal carcinoma) Intraoperative peritoneal cancer index (PCI) ≤ 15 for gastric carcinoma and ≤ 20 for colon carcinoma. Possibility of surgical resection of peritoneal carcinomatosis (cytoreductive surgery) in curative intention with achievement of a Completeness of Cytoreduction Score (CCS) of 0-1 No contraindication to surgery No contraindication against the performance of HIPEC Expected survival of 6 months at least ECOG ≤ 2 Female and male patients ≥ 18 years of age Patient is able and willing to give written informed consent and comply with the study protocol Exclusion Criteria: Presence of non-resectable distant metastases Patients with extensive metastasis (e.g., multiple bilobular liver metastases, hepatic and pulmonary metastases, multiple retroperitoneal lymph node metastases; oligometastasis is allowed) Patients with recurrence of peritoneal carcinomatosis (e.g., previous peritonectomy in the course of primary tumor resection) Patients after previous palliative chemotherapy or radiation of the tumor (exception: neoadjuvant and/or adjuvant therapies) Hypersensitivity/allergy to components of the planned intraperitoneal chemotherapy Patients not eligible for surgery/HIPEC (e.g., heart failure NYHA ≥III, myocardial infarction within the last 3 months before surgery, high-risk cardiac arrhythmias) Secondary malignant disease that occurred <5 years ago (exception: early stage of a localized tumor with in-sano resection, for example in situ carcinoma of the cervix, Adequately treated basal cell carcinoma of the skin) Patients who are housed in a closed facility Pregnant or breastfeeding patients, or patients who plan to become pregnant within 7 Months after the end of treatment to become pregnant

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

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

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

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

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Establishment of organoid cultures and in vitro sensitivity testing|Generating patient-derived tumor organoid models as well as orthotopic mouse models from peritoneal carcinomatosis lesions and to investigate their response to different therapies.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the sensitivity of the in vitro response of the organoid model to chemotherapeutic agents | Organoid treatment by means of ascending doses of chemotherapy and under HIPEC conditions, i.e. with elevated temperature | 1 year | 
| Next generation sequencing of organoid cultures | Sequencing of DNA and RNA (Ribonucleic acid) | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Organoid