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

NCT06057298 | Unknown

• 2 other identifiers: INT 0006/21RF-2019-12370456
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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;

Conditions

Peritoneal Metastases From Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Feasibility of patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

  48 months

• Overall survival

  60 months

• Disease-free survival

  60 months

• Safety of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

  48 months

Study Arms (1)

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

EXPERIMENTAL

* 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)

Interventions

Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC) PROCEDURE

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)

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• active sepsis;
• impaired cardiac function (history of previous heart failure or 40% ejection fraction);
• impaired renal function (serum creatinine \>1.5 normal value or creatinine clearance \< 60 ml/min);
• impaired liver function (aspartate aminotransferase, alanine aminotransferase, bilirubin \> 1.5 normal value);
• impaired bone marrow function (leukocytes \<4000/mm3, neutrophils \<1500/mm3, platelets \<80000/mm3);
• 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);
• dehydropyrimidine dehydrogenase deficiency;
• pregnancy or lactation in progress;
• haemorrhagic diathesis or coagulopathy;
• 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);
• psychiatric or neurological conditions that preclude the procedures of the protocol;
• any contraindication to laparoscopy;
• known hypersensitivity to any of the chemotherapy agents used for HIPEC in the present study and/or to any of their excipients;
• history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma;
• previous cytoreductive surgery and HIPEC

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (2)

• 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.

  PMID: 36460033 BACKGROUND

• 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.

  PMID: 37500685 BACKGROUND

Study Officials

• Dario Baratti, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dario Baratti, MD

CONTACT

+390223901; dario.baratti@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: September 28, 2023
• Study Start: June 15, 2021
• Primary Completion: June 14, 2025
• Study Completion: June 14, 2025
• Last Updated: October 24, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: after the completion of the study, for additional 60 months
• Access Criteria: upon reasonable request to the principal investigator

Locations

IT (1)