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

Peritoneal Metastases From Colorectal Cancer Clinical Trial

— OrganoHIPEC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06057298
• Other study ID #: INT 0006/21
• Secondary ID: RF-2019-12370456
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2021
• Est. completion date: June 14, 2025

Study information

• Verified date: September 2023
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: Dario Baratti, MD
• Phone: +390223901
• Email: dario.baratti[@]istitutotumori.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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;

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 14, 2025
• Est. primary completion date: June 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Peritoneal Metastases From Colorectal Cancer

Intervention

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)

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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