Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status: Enrolling

Conditions: Peritoneal Metastases From Colorectal Cancer

Treatments: Procedure: Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

Study type: Interventional

Funder types: Other

Identifiers

NCT06057298

RF-2019-12370456 (Other Grant/Funding Number)

INT 0006/21

Details and patient eligibility

About

The objective of this clinical trial is to demonstrate that cytoreductive surgery and patient-tailored hyperthermic intra-peritoneal chemotherapy (HIPEC) will increase efficacy in controlling peritoneal disease. Tridimensional cell cultures (organoids) derived from colorectal cancer peritoneal metastases are used to select the most active drugs in an in vitro HIPEC model on individual-patient level, based on the hypothesis that resistance to drug(s) routinely used for intraperitoneal delivery can explain peritoneal relapse after combined treatment, depending on the individual tumor biology;

Full description

This single-arm, single-center, open-label trial enrolls patients with limited and surgically resectable peritoneal metastases from colorectal cancer, no distant metastases, and no contraindication to major surgery. After signature of informed consent, patients undergo a preliminary laparoscopy to confirm diagnosis of peritoneal metastases, stage the disease, and obtain representative samples of peritoneal metastases. The investigators will use patient-derived organoids to select tailored hyperthermic intra-peritoneal chemotherapy (HIPEC) regimens in an in vitro model HIPEC. A set of candidate drugs suitable for intraperitoneal administration are tested on tumor-derived organoids under the same conditions as in the clinical practice (same drug combinations, concentration, exposure time, temperature). Different concentrations are tested to generate reproducible dose-response curves. Patients receive 3-6 month preoperative systemic chemotherapy with targeted agents, according to current guidelines. Those not experiencing disease progression during preoperative systemic chemotherapy will have cytoreductive surgery and HIPEC with drugs selected on the organoid-based preclinical model. Patients will undergo postoperative follow-up.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. diagnosis of peritoneal metastases from intestinal-type or mucinous colo-rectal adenocarcinoma, by histological/cytological confirmation.
2. limited to moderate peritoneal involvement: peritoneal cancer index (PCI) ≤ 20;
3. peritoneal disease potentially amenable to complete surgical cytoreduction;
4. no evidence of hepatic, extra-regional nodal, or extra abdominal metastases
5. World Health Organization (WHO) performance status ≤2;
6. willingness to undergo preliminary laparoscopy, perioperative s-CT, and post-operative follow-up;
7. signature of informed consent.

Exclusion criteria

1. active sepsis;
2. impaired cardiac function (history of previous heart failure or 40% ejection fraction);
3. impaired renal function (serum creatinine >1.5 normal value or creatinine clearance < 60 ml/min);
4. impaired liver function (aspartate aminotransferase, alanine aminotransferase, bilirubin > 1.5 normal value);
5. impaired bone marrow function (leukocytes <4000/mm3, neutrophils <1500/mm3, platelets <80000/mm3);
6. impaired lung function (diagnosis of severe chronic obstructive pulmonary disease or 50% forced expiratory volume at one second or 40% diffusion capacity of lung for carbon monoxide adjusted for age);
7. dehydropyrimidine dehydrogenase deficiency;
8. pregnancy or lactation in progress;
9. haemorrhagic diathesis or coagulopathy;
10. any other condition or comorbidity that prevents safe administration of systemic chemotherapy (e.g. severe diarrhea, stomatitis or ulceration in the mouth or gastrointestinal tract);
11. psychiatric or neurological conditions that preclude the procedures of the protocol;
12. any contraindication to laparoscopy;
13. known hypersensitivity to any of the chemotherapy agents used for HIPEC in the present study and/or to any of their excipients;
14. history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma;
15. previous cytoreductive surgery and HIPEC

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Cytoreductive surgery and patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Experimental group

Description:

* Preliminary laparoscopic exploration of the whole abdominal cavity is performed to stage the peritoneal disease, and obtain samples of peritoneal tumor to confirm the diagnosis of colorectal peritoneal metastases, and develop tridimensional cell cultures (organoids). * Preoperative systemic chemotherapy (s-CT) is performed at the discretion of treating medical oncologists, according to current guidelines. * Cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC) is scheduled within 6 weeks and at least 4 weeks after the completion of preoperative s-CT (at least 6 weeks after the last administration of bevacizumab). Cytoreductive surgery is aimed at removing all the macroscopic tumor by means od peritonectomy procedures and organ resections, as needed.

Treatment:

Procedure: Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)