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

NCT ID: NCT06057298

Last Updated: 2023-10-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2025-06-14

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.

Conditions

Peritoneal Metastases From Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

Intervention Type: 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)

Interventions

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)

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dario Baratti, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Dario Baratti, MD

Role: CONTACT

dario.baratti@istitutotumori.mi.it

+390223901 ext. 3441

Facility Contacts

Dario Baratti, MD

Role: primary

dario.baratti@istitutotumori.mi.it

+390223903441

References

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.

Reference Type: BACKGROUND

PMID: 36460033 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37500685 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

RF-2019-12370456

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

INT 0006/21

Identifier Type: -

Identifier Source: org_study_id