HIPEC Using High Intra-abdominal Pressure

NCT02949791 | Completed Phase 2 DMC

• 1 other identifier: AIRC-2013-144445
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising therapy for peritoneal carcinomatosis (PC) of various origins. Rather than the pharmacokinetic advantage, the uptake of chemotherapy by tumor tissue has been proposed as the best pharmacologic endpoint to assure the efficacy of HIPEC. The primary endpoints of the present phase II randomized study are to test whether the increased intra abdominal pressure (IAP) during HIPEC could:

• enhance the penetration of cisplatin into the residual neoplastic and normal tissues;
• elicit changes on pharmacokinetic advantage of cisplatin. Secondary endpoints are to evaluate the:
• impact of high IAP on intraoperatory hemodynamic and respiratory parameters;
• impact on short-term surgical outcomes (in hospital stay, morbidity, mortality). Patients affected by PC from colorectal cancer or pseudomyxoma peritonei, submitted to complete cytoreduction (residual disease \<2.5mm) would be eligible for the study. HIPEC will be performed using closed abdomen technique and cisplatin + mitomycin-C. Patients will be randomly assigned to HIPEC with low IAP (8-12 mmHg) or high IAP (18-22 mmHg). IAP will be measured using bladder catheter. High IAP will be obtained increasing the volume of perfusate. Thirty-eight patients (19 in each study groups) will be enrolled in 30 months. The randomized groups will be stratified according to tumor type.

Conditions

Pseudomyxoma Peritonei; Colorectal Cancer

Keywords

cisplatin; HIPEC; Intra abdominal pressure; tissue drug concentration

Outcome Measures

Primary Outcomes (2)

• Tumor tissue concentration of cisplatin

  residual neoplastic tissue concentration of cisplatin measured in ng/mg

  collected within 15 minutes after the completion of HIPEC

• Normal tissue concentration of cisplatin

  tissue concentration of cisplatin measured in ng/mg in peritoneum of mesentery and rectal muscle fascia

  collected within 15 minutes after the completion of HIPEC

Secondary Outcomes (11)

• Pharmacokinetic advantage

  During the HIPEC up to 1 hour from the completion of perfusion

• Pharmacokinetic advantage 2

  During the HIPEC up to 1 hour from the completion of perfusion

• Impact of high intra-abdominal pressure on anesthesiologic parameters 1

  Intraoperative phase

• Impact of high intra-abdominal pressure on anesthesiologic parameters 2

  Intraoperative phase

• Impact of high intra-abdominal pressure on anesthesiologic parameters 3

  Intraoperative phase

Study Arms (2)

Low Intra abdominal pressure HIPEC

ACTIVE COMPARATOR

Cytoreductive surgery and HIPEC with low intra-abdominal pressure

Procedure: Cytoreductive surgery; Other: Low Intra abdominal pressure HIPEC

High Intra abdominal pressure HIPEC

EXPERIMENTAL

Cytoreductive surgery and HIPEC with high intra-abdominal pressure

Procedure: Cytoreductive surgery; Other: High Intra abdominal pressure HIPEC

Interventions

Cytoreductive surgery PROCEDURE

Maximal surgical effort to obtain a minimal residual disease of less than 2.5 mm

Also known as: Peritonectomy procedures

High Intra abdominal pressure HIPEC; Low Intra abdominal pressure HIPEC

Low Intra abdominal pressure HIPEC OTHER

Hyperthermic intraperitoneal chemotherapy using closed modality and intra abdominal pressure of 8-12 mmHg

Low Intra abdominal pressure HIPEC

High Intra abdominal pressure HIPEC OTHER

Hyperthermic intraperitoneal chemotherapy using closed modality and intra abdominal pressure of 18-22 mmHg

High Intra abdominal pressure 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:

• Histological diagnosis of primary peritoneal carcinomatosis from colorectal origin or pseudomyxoma peritonei
• Patients submitted to complete cytoreduction with residual tumor \<2.5 mm
• Patients at the end of cytoreduction should present the laboratorial and hemodynamic parameters set as followings:
• Mean arterial pressure \> 65 mmHg
• Heart rate: \< 100 bpm
• Central venous pressure \> 4 mmHg
• Cardiac index \> 2.2
• Central venous oxygen saturation (ScvO2) \> 72%, and
• Haemoglobin \> 8.0 gr/dl.
• Informed consent signed from the patient before the procedure.

You may not qualify if:

• Severe hemodynamic and/or respiratory instability after the cytoreduction that precludes HIPEC.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, MI, 20133, Italy

Location

Related Publications (7)

• Esquis P, Consolo D, Magnin G, Pointaire P, Moretto P, Ynsa MD, Beltramo JL, Drogoul C, Simonet M, Benoit L, Rat P, Chauffert B. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg. 2006 Jul;244(1):106-12. doi: 10.1097/01.sla.0000218089.61635.5f.

  PMID: 16794395 BACKGROUND

• Facy O, Al Samman S, Magnin G, Ghiringhelli F, Ladoire S, Chauffert B, Rat P, Ortega-Deballon P. High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study. Ann Surg. 2012 Dec;256(6):1084-8. doi: 10.1097/SLA.0b013e3182582b38.

  PMID: 22634898 BACKGROUND

• Facy O, Combier C, Poussier M, Magnin G, Ladoire S, Ghiringhelli F, Chauffert B, Rat P, Ortega-Deballon P. High pressure does not counterbalance the advantages of open techniques over closed techniques during heated intraperitoneal chemotherapy with oxaliplatin. Surgery. 2015 Jan;157(1):72-8. doi: 10.1016/j.surg.2014.06.006. Epub 2014 Jul 12.

  PMID: 25027716 BACKGROUND

• Rossi CR, Foletto M, Mocellin S, Pilati P, De SM, Deraco M, Cavaliere F, Palatini P, Guasti F, Scalerta R, Lise M. Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study. Cancer. 2002 Jan 15;94(2):492-9. doi: 10.1002/cncr.10176.

  PMID: 11900234 BACKGROUND

• Jacquet P, Stuart OA, Chang D, Sugarbaker PH. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs. 1996 Jul;7(5):596-603. doi: 10.1097/00001813-199607000-00016.

  PMID: 8862729 BACKGROUND

• Van der Speeten K, Stuart OA, Sugarbaker PH. Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy. Cancer J. 2009 May-Jun;15(3):216-24. doi: 10.1097/PPO.0b013e3181a58d95.

  PMID: 19556908 BACKGROUND

• Kusamura S, Azmi N, Fumagalli L, Baratti D, Guaglio M, Cavalleri A, Garrone G, Battaglia L, Barretta F, Deraco M. Phase II randomized study on tissue distribution and pharmacokinetics of cisplatin according to different levels of intra-abdominal pressure (IAP) during HIPEC (NCT02949791). Eur J Surg Oncol. 2021 Jan;47(1):82-88. doi: 10.1016/j.ejso.2019.06.022. Epub 2019 Jun 21.

  PMID: 31262599 DERIVED

MeSH Terms

Conditions

Pseudomyxoma Peritonei; Colorectal Neoplasms

Interventions

Cytoreduction Surgical Procedures

Condition Hierarchy (Ancestors)

Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Shigeki Kusamura, MD PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.Shigeki Kusamura

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 31, 2016
• Study Start: December 1, 2014
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: February 23, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)