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

Organoids From Colorectal Peritoneal Metastases to Improve Cytoreductive Surgery and Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

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;

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Metastases From Colorectal Cancer
• Intervention / Treatment: Procedure: Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dario Baratti, MD; Phone Number: 3441 +390223901; Email: dario.baratti@istitutotumori.mi.it

Study Locations

• Italy
  • Milano, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Contact: Dario Baratti, MD; Phone Number: +390223903441; Email: dario.baratti@istitutotumori.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cytoreductive surgery and patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC); 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.

Procedure: Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC); Patient-tailored HIPEC is performed by the closed-abdomen technique with the following drugs selected according to the results of the sensitivity tests on the organoid-based preclinical model: Oxaliplatin 360 mg/mq for 30 min.; Oxaliplatin 200 mg/mq for 120 min.; Mitomycin-C 35mg/mq for 60 min.; Mitomycin-C 3.3 mg/mq/l of perfusate + cisplatin 25 mg/mq/l of perfusate for 60 min. (perfusate volume l. 4-6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year peritoneal metastasis-free survival	Proportion of patients who remain free of peritoneal metastasis at a time interval of one year from the date of the combined procedure of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)	Feasibility will be determined as the number of patients who have cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC) among the total number of patients selected to be included in the study who sign the informed consent form	48 months
Overall survival	Overall survival will be measured from the date of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC) to the date of death for any cause or, for patients still alive at the date of the last available follow-up	60 months
Disease-free survival	Disease-free survival will be measured from the date of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC) to the date of peritoneal metastasis diagnosis, systemic metastases or death.	60 months
Safety of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)	Proportion of patients who will suffer from postoperative complications after cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)	48 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Dario Baratti, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Estimated): June 14, 2025
• Study Completion (Estimated): June 14, 2025

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: INT 0006/21; RF-2019-12370456 (Other Grant/Funding Number: Italian Health Minister Ricerca Finalizzata)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: I confirm that we have a plan to make individual participant data (IPD) available to other researchers through publicly available database
• IPD Sharing Time Frame: after the completion of the study, for additional 60 months
• IPD Sharing Access Criteria: upon reasonable request to the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No