Clinical trial NCT06057298: Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)
Official title: Organoids From Colorectal Peritoneal Metastases to Improve Cytoreductive Surgery and Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peritoneal Metastases From Colorectal Cancer
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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;

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: One-year peritoneal metastasis-free survival
timeFrame: 12 months
Secondary outcomes:
measure: Feasibility of patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
timeFrame: 48 months
measure: Overall survival
timeFrame: 60 months
measure: Disease-free survival
timeFrame: 60 months
measure: Safety of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
timeFrame: 48 months
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
name: Dario Baratti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Varinelli L, Guaglio M, Brich S, Zanutto S, Belfiore A, Zanardi F, Iannelli F, Oldani A, Costa E, Chighizola M, Lorenc E, Minardi SP, Fortuzzi S, Filugelli M, Garzone G, Pisati F, Vecchi M, Pruneri G, Kusamura S, Baratti D, Cattaneo L, Parazzoli D, Podesta A, Milione M, Deraco M, Pierotti MA, Gariboldi M. Decellularized extracellular matrix as scaffold for cancer organoid cultures of colorectal peritoneal metastases. J Mol Cell Biol. 2023 Apr 6;14(11):mjac064. doi: 10.1093/jmcb/mjac064.
citation: Lorenc E, Varinelli L, Chighizola M, Brich S, Pisati F, Guaglio M, Baratti D, Deraco M, Gariboldi M, Podesta A. Correlation between biological and mechanical properties of extracellular matrix from colorectal peritoneal metastases in human tissues. Sci Rep. 2023 Jul 27;13(1):12175. doi: 10.1038/s41598-023-38763-w.