Neoplasms

Symptoms and General Pathology

All Conditions

Wounds and Injuries

Neoplasm Metastasis

Hyperthermia

Fever

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Bevacizumab

Cisplatin

Mitomycins

Mitomycin

* 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.

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)

Patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

Dario Baratti, MD

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;

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.

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

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

I confirm that we have a plan to make individual participant data (IPD) available to other researchers through publicly available database

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)

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 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 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.

Proportion of patients who will suffer from postoperative complications after cytoreductive surgery and patient-tailored hyperthermic intraperitoneal chemotherapy (HIPEC)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Capecitabine

Raltitrexed

HIPEC with Raltitrexed at the time of fist surgery and twice repeat within one week after the surgery, following 3 cycles of 3-week Oxaliplatin/Capecitabine chemotherapy. The second surgery, exploratory laparoscopy or laparotomy, is carried out one week later after the series of systemic chemotherapy.

Exploratory laparoscopy or laparotomy, for PCI score or radical colorectal resection and cytoreductive surgery

exploratory laparoscopy or laparotomy

Normal saline 3000ml-4000ml, Raltitrexed 4mg, 43°C, 60min.

HIPEC

Oxaliplatin: 130mg/m2, day 1. Capecitabine: 1500mg, twice daily for two weeks, and then suspend for one week

Systemic chemotherapy

The prognosis of patients with unresectable peritoneal metastases from colorectal cancer is poor. These patients may obtain survival benefit from radical colorectal resection and cytoreductive surgery (CRS). The response rates of previous conversion therapy are low. Hyperthermic intraperitoneal chemoperfusion (HIPEC) and systemic chemotherapy are effective methods of reducing peritoneal cancer index (PCI) levels. The purpose of this study is to investigate the efficacy and safety of HIPEC and systemic chemotherapy in the conversion therapy of peritoneal metastases from colorectal cancer.

To determine the efficacy and safety of HIPEC and systemic chemotherapy in the conversion therapy of peritoneal metastases from colorectal cancer, patients undergo HIPEC with Raltitrexed at the time of fist surgery and twice repeat within one week after the surgery, following 3 cycles of 3-week Oxaliplatin/Capecitabine chemotherapy. The second surgery, exploratory laparoscopy or laparotomy, is carried out one week later after the series of systemic chemotherapy.

HIPEC and Systemic Chemotherapy in Unresectable Peritoneal Metastases From Colorectal Cancer

A Study of Conversion Therapy Using Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) and Systemic Oxaliplatin/Capecitabine Chemotherapy in Unresectable Peritoneal Metastases From Colorectal Cancer

The rate between the number of patients with radically resectable peritoneal metastases and those with unresectable peritoneal metastases

The score range from 0 to 39, higher values represent a worse outcome

Wuhan University

Zhongnan Hospital

Micronutrients

Pharmaceutical Solutions

Hematinics

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Folic Acid

Folinic Acid

Folate

Vitamin B9

Preliminary laparoscopic exploration of the abdominal cavity and adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin and concurrent intravenous infusion of 5-fluorouracil and folinic acid.

Laparoscopic exploration of the abdominal cavity with dissection of adhesions and biopsies of suspect findings (if needed).

PIPAC will be administered with oxaliplatin (92 mg/m2 body surface area in 150 ml dextrose solution) for 30 minutes under the following spraying conditions: cytostatic application at a rate of 30 ml/min, pressure of 1380 kilo-pascal over 30 minutes, and temperature of 22°C. One hour before the beginning of PIPAC, intravenous infusion of 5-fluorouracil (400 mg/m2) and folinic acid (20mg/m2) will be initiated. Standard protectionist procedures will be adopted to avoid contamination of operators and the environment with nebulized chemotherapy.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

The objective of this clinical trial is to demonstrate the feasibility and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for the prevention of peritoneal metastases after curative-intent surgery for high-risk colorectal cancer.

This single-arm, single-center, open-label trial enrolls patients after curative-intent surgery for colon adenocarcinoma (proximal to peritoneal reflection), intestinal or mucinous histological type, associated with the following clinical-pathological risk factors for the development of peritoneal metastases: a) stage pT4a, N0-2b, M0 of the Tumor Node Metastasis classification; b) stage pT4b, N0-2b, M0; and c) primary perforated tumor (any T, any N, M0). Eligible patients who will give informed consent undergo laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC) 4 to 8 weeks after primary surgery, followed by adjuvant systemic chemotherapy according to according to current guidelines. After the procedure, patients will be followed-up to assess occurrence of adverse events,survival, peritoneal and systemic disease relapse, and quality of life.

Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC)

Pilot Study of Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for the Prevention of Peritoneal Metastases After Curative-intent Surgery for High-risk Colorectal Cancer.

The adjuvant PIPAC performed in an early setting after primary surgery will be considered feasible if:

* the laparoscopic procedure can be completed in 9 patients;
* the postoperative stay will be three days or shorter in ≥6 patients;
* the post-operative adjuvant s-CT will begin within 12 weeks of primary surgery in ≥ 9 patients.

The adjuvant PIPAC will be considered a well tolerated procedure if:

* a maximum of one serious treatment-related complication will occur;
* a maximum of one laparotomy conversion will occur;
* a maximum of one hospital readmission will occur within 30 days.

Overall survival will be measured from the date of primary surgery 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 will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis, systemic metastases or death.

Peritoneal disease-free survival will be measured from the date of primary surgery to the date of peritoneal metastasis diagnosis,

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)	NCT06057298	Peritoneal Meta...	Patient-tailore...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
HIPEC and Systemic Chemotherapy in Unresectable Peritoneal Metastases From Colorectal Cancer	NCT03398512	Peritoneal Meta...	exploratory lap... HIPEC Systemic chemot...	18 Years - 75 Years	Wuhan University
Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC)	NCT06091683	Peritoneal Meta...	Pressurized int...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC)	NCT06091683	Peritoneal Meta...	Pressurized int...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)	NCT06057298	Peritoneal Meta...	Patient-tailore...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for peritoneal metastases from colorectal cancer