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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT01685632
First received: September 12, 2012
Last updated: NA
Last verified: September 2012
History: No changes posted
  Purpose

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.


Condition Intervention
Peritoneal Carcinomatosis From Colorectal or Ovarian Origin
Procedure: Surgery with IPCH
Procedure: Without surgery and without IPCH

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Intra Peritoneal Chemo Hyperthermia (IPCH) : Cellular and Metabolic Consequences

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • heat shock protein expression (blood/cell ratio)compared to baseline values [ Time Frame: samples taken under general anesthesia throughout surgery and during the 3 following days (24h, 48h,72h) ] [ Designated as safety issue: No ]
    • 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.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685632

Locations
France
Département d'Anesthésie Réanimation, CHU de Nice
Nice, France, 06200
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Principal Investigator: Michel CARLES, PhD Anesthesia Department, CHU de NICE
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT01685632     History of Changes
Other Study ID Numbers: 11-PP-01
Study First Received: September 12, 2012
Last Updated: September 12, 2012
Health Authority: France: Institutional Ethical Committee

Keywords provided by Centre Hospitalier Universitaire de Nice:
intra peritonal chemo hyperthermia
peritoneal carcinomatosis
colorectal cancer
ovarian cancer

Additional relevant MeSH terms:
Fever
Carcinoma
Body Temperature Changes
Signs and Symptoms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 23, 2014