Intra Peritoneal Chemo Hyperthermia (IPCH) : Cellular and Metabolic Consequences (CHIP)

Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the disease. From a clinical point of view, within the first 24 hours after IPCH, patients undergo a systemic inflammatory response syndrome, and therefore require to be monitored in an intensive care unit. From a metabolic perspective, preliminary data have been shown a significant "anaerobic style" disturbance of energetic metabolism, suggesting a deep cellular energetic deficit throughout IPCH process.

Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular toxicity due to heat and on the other hand the initiation of a stress protein response (heat shock response) which helps to reduce the cell injuries, leads to conduct a research project on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of high relevance.

The primary goal is a multimodal assessment of the IPCH-related cell modifications: signaling pathways, apoptosis and antitumoral immune response.

The assessment criteria include Heat shock protein expression (blood/cell ratio) compared to baseline values, apoptosis and immune response before/after IPCH.

The scheduled sample size is 30 patients having an IPCH and 30 patients contraindicated per surgery.

Study Overview

• Status: Terminated
• Conditions: Peritoneal Carcinomatosis From Colorectal or Ovarian Origin
• Intervention / Treatment: Procedure: Surgery with IPCH; Procedure: Without surgery and without IPCH

Detailed Description

Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the disease (survival median > 33 months). IPCH induces morbidity as high as 20% and mortality less than 4%. From a clinical point of view, within the first 24 hours after IPCH, patients undergo a systemic inflammatory response syndrome, and therefore require to be monitored in an intensive care unit. From a metabolic perspective, preliminary data have been shown a significant "anaerobic style" disturbance of energetic metabolism, suggesting a deep cellular energetic deficit throughout IPCH process.

Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular toxicity due to heat and on the other hand the initiation of a stress protein response (heat shock response) which helps to reduce the cell injuries, leads to conduct a research project on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of high relevance.

Heat shock protein expression (stress protein response markers) and apoptosis are the main chosen tools to evaluate IPCH-related cellular consequences.

Goals of the study Primary goal Multimodal assessment of the IPCH-related cell modifications: signaling pathways, apoptosis and antitumoral immune response.

Secondary goal Comparative study of Heat shock protein expression, whether IPCH is done or the patient is recused for the surgery due to intraoperative contraindication.

Method Prospective cohort follow up Procedure

Besides the usual care (surgical debulking and extensive tumoral resection after laparotomy under general anesthesia), the research protocol includes :

• 7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).
• 6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH.

Assessment criteria

• main criteria : Heat shock protein expression (blood/cell ratio) compared to baseline values.
• associate criteria : apoptosis and immune response before/after IPCH Statistical method/Sample size/Study's lenght Scheduled sample size is 30 patients having an IPCH and 30 patients contraindicated per surgery.

The normal distribution is verified using the d'Agostino-Pearson test. For intragroup comparisons, the repeated measures ANOVA is done. For intergroup comparisons, an univariate analysis is done, using the Student t-test and the Fisher exact test.

Taking into account the planned sample size and the annual number of IPCH, the scheduled length of the study is 18 months.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France, 06200
    • Département d'Anesthésie Réanimation, CHU de Nice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patient
• eligible for IPCH
• with a social security number
• having a signed an informed consent

Exclusion Criteria:

• study refusal
• parturiants
• psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgery with IPCH; Patients having an IPCH (Intra Peritoneal Chemo Hyperthermia) during the surgery time	Procedure: Surgery with IPCH; surgical debulking and extensive tumoral resection after laparotomy under general anesthesia; 7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).; 6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH
Sham Comparator: patients without IPCH; Patients recused for the surgery due to intraoperative contraindication	Procedure: Without surgery and without IPCH; The patients is opened and recused during the surgery because of extended carcinosis and closed without resection neither IPCH.; 7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery (2 hours before IPCH, 1.5hours after IPCH, 4 hours after IPCH) and 3 samples during the 3 following days (at 24th, 48th and 72th hours).; 6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum, each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
heat shock protein expression (blood/cell ratio)compared to baseline values	7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).; 6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH.	samples taken under general anesthesia throughout surgery and during the 3 following days (24h, 48h,72h)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Michel CARLES, PhD, Anesthesia Department, CHU de NICE

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: September 12, 2012
• First Submitted That Met QC Criteria: September 12, 2012
• First Posted (Estimate): September 14, 2012

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: colorectal cancer; ovarian cancer; peritoneal carcinomatosis; intra peritonal chemo hyperthermia
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Wounds and Injuries; Digestive System Neoplasms; Abdominal Neoplasms; Body Temperature Changes; Heat Stress Disorders; Carcinoma; Peritoneal Neoplasms; Hyperthermia; Fever
• Other Study ID Numbers: 11-PP-01