Back to resultsPatient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC) (OrganoHIPEC)
Primary Purpose
Peritoneal Metastases From Colorectal Cancer
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
Sponsored by
About this trial
This is an interventional treatment trial for Peritoneal Metastases From Colorectal Cancer
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Sites / Locations
- Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cytoreductive surgery and patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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
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
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.
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)
Full Information
NCT ID
NCT06057298
First Posted
September 21, 2023
Last Updated
October 20, 2023
Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1. Study Identification
Unique Protocol Identification Number
NCT06057298
Brief Title
Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)
Acronym
OrganoHIPEC
Official Title
Organoids From Colorectal Peritoneal Metastases to Improve Cytoreductive Surgery and Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
June 14, 2025 (Anticipated)
Study Completion Date
June 14, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Metastases From Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cytoreductive surgery and patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
Intervention Description
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)
Primary Outcome Measure Information:
Title
One-year peritoneal metastasis-free survival
Description
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)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Feasibility of patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
Description
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
Time Frame
48 months
Title
Overall survival
Description
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
Time Frame
60 months
Title
Disease-free survival
Description
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.
Time Frame
60 months
Title
Safety of cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
Description
Proportion of patients who will suffer from postoperative complications after cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)
Time Frame
48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dario Baratti, MD
Phone
+390223901
Ext
3441
Email
dario.baratti@istitutotumori.mi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dario Baratti, MD
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dario Baratti, MD
Phone
+390223903441
Email
dario.baratti@istitutotumori.mi.it
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
36460033
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.
Results Reference
background
PubMed Identifier
37500685
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.
Results Reference
background
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Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)
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