Elimination of Peritoneal Tumor Cells With Extensive Peritoneal Lavage During Surgery in Patients With Gastric Cancer (EIPL)

This study has been terminated.
(Prematurely halted after interim data analysis)
Sponsor:
Collaborator:
Heidelberg University
Information provided by (Responsible Party):
Ulrich Ronellenfitsch, MD, University Hospital Mannheim
ClinicalTrials.gov Identifier:
NCT01476553
First received: November 11, 2011
Last updated: March 21, 2013
Last verified: March 2013
  Purpose

A Japanese study showed that the additional use of an "Extensive Intraperitoneal Lavage" (EIPL), i.e. an extensive washing of the abdominal cavity with water, during surgery for gastric cancer can lead to a significant increase in survival. However, the study was confined to patients in whom upon commencing surgery, free peritoneal tumor cells were detected, which is only a small fraction of patients.

The primary objective of our study is to assess in all patients undergoing removal of the stomach and adjacent lymph nodes for stomach cancer, if EIPL can eliminate free peritoneal tumor cells which have been present at the beginning of the surgery or after the stomach and lymph node removal. Secondary objectives are to assess how often free peritoneal tumor cells occur in patients with stomach cancer, how often surgical resection itself leads to a release of tumor cells, the safety of the EIPL procedure, and disease-free and overall survival of patients undergoing EIPL. Based on the outcome of this japanese study we want to test with special laboratory methods why this lavage leads to a better outcome.

Specifically, the trial will test the hypotheses that a) lymph node dissection causes a release of tumor cells in the abdominal cavity, and b) EIPL eliminates free peritoneal tumor cells.


Condition Intervention
Adenocarcinoma
Stomach Neoplasms
Procedure: Extensive Intraperitoneal Lavage (EIPL)

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Elimination of Peritoneal Tumor Cells With "Extensive Intraperitoneal Lavage (EIPL)" During Surgical Treatment of Gastric Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Universitätsmedizin Mannheim:

Primary Outcome Measures:
  • Peritoneal Conversion Rate (PCR) [ Time Frame: intraoperative (day of surgery) ] [ Designated as safety issue: No ]
    The Peritoneal Conversion Rate (PCR) is defined as the proportion of patients in whom no free peritoneal tumor cells are detected after EIPL among all patients in whom free peritoneal tumor cells were detected before EIPL. In other words, the PCR measures in what proportion of patients EIPL leads to an elimination of intraperitoneal tumor cells.


Secondary Outcome Measures:
  • Peritoneal Release Rate (PRR) [ Time Frame: intraoperative (day of surgery) ] [ Designated as safety issue: No ]
    The Peritoneal Release Rate (PRR) is defined as the proportion of patients in whom free peritoneal tumor cells are detected after gastrectomy and lymphadenectomy among all patients in whom no free peritoneal tumor cells were detected before gastrectomy and lymphadnectomy. In other words, this denotes the proportion of patients in whom tumor cells are released into the peritoneal cavity due to the surgical measures performed.

  • Prevalence of free peritoneal tumor cells before resection [ Time Frame: intraoperative (day of surgery) ] [ Designated as safety issue: No ]
    This denotes the proportion of patients in whom free intraperitoneal tumor cells can be detected upon laparotomy among all operated patients.

  • Overall Survival [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time between surgery and death, independent of the cause of death.

  • Recurrence-free survival [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    Recurrence-free survival is defined as the time between surgery and the appearance of a local recurrence, peritoneal carcinomatosis, or distant metastases.

  • Perioperative in-hospital morbidity [ Time Frame: up to the end of the hospital stay (estimated average two weeks after surgery) ] [ Designated as safety issue: Yes ]
    All complications occuring throughout the hospital stay of the patient are assessed according to the Clavien-Dindo classification for surgical complications (6).


Estimated Enrollment: 64
Study Start Date: February 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Extensive Intraperitoneal Lavage (EIPL)

    EIPL is performed after completing resection and lymphadenectomy: the abdominal cavity has to be washed ten times with one liter Ringer's solution. Each liter has to be well dispersed manually in the abdominal cavity, and removed and disposed completely. 100 ml of the last liter of lavage fluid will be harvested and sent for analysis.

    Contrary to the Japanese trial, Ringer's solution will be used instead of normal saline solution because of a presumed higher likelihood of peritoneal adhesions when employing the latter (7). Ringer's solution is the standard used for all intraperitoneal lavage procedures at the study centre. To avoid hypothermia, the lavage fluid will be warmed to body temperature (37° Celsius).

    Other Names:
    • EIPL
    • extensive intraperitoneal lavage
    • lavage
Detailed Description:

In spite of the existence of multimodal therapy, the long-term survival of patients with gastric cancer remains poor. In advanced tumor stages, five-year survival rates rarely exceed 30%. One of the factors limiting overall survival is peritoneal carcinomatosis, which frequently occurs after surgical treatment with curative intention.

Peritoneal carcinomatosis is supposed to develop from peritoneal implantation of tumor cells already present in the abdominal cavity during primary surgery. It is assumed that both serosal tumor infiltration and intraoperative lymphadenectomy, which per se leads to a survival improvement (1) and is therefore considered standard in Europe and Japan ((2), http://www.jpca.jp/PDFfiles/ Guidelines2004_eng.pdf), can release tumor cells into the peritoneal cavity. Of note, a Japanese study found that tumor cells were released into the peritoneal cavity during lymphadenectomy in 14-46% of patients, depending on preoperative tumor stage (3).

A randomized clinical trial from Japan (4) demonstrated that an "extensive intraperitoneal lavage" (EIPL), i.e. an irrigation of the abdominal cavity with ten times one liter of physiological saline solution, in combination with intraperitoneal chemotherapy (IPC) carried out after gastrectomy and lymphadenectomy, led to a significant improvement in overall survival compared to patients who received only surgery and IPC without EIPL, and those who received surgery alone without EIPL and IPC. These results suggest that the largest survival benefit is attributable to the addition of EIPL to IPC (5-year survival rate: 43.8% vs. 4.6%) and not to the addition of IPC to surgery alone (5-year survival rate: 4.6% vs. 0%).

However, it is important to consider that the study included only patients in whom peritoneal tumor cells were detected before resection of the stomach and lymph nodes. Thus, only 90 of 1522 (5.9%) patients operated in the participating centers throughout the study period fulfilled the inclusion criteria. Furthermore, the study design was not appropriate to assess if EIPL really leads to a reduction of free tumor cells as assumed. Regarding this hypothesis, the only available results stem from single patients out of smaller studies (4;5). To date, there is no higher level evidence from larger populations.

The present trial, for the first time, uses EIPL as additional treatment in patients with any tumor stage and regardless of the detection of intraperitoneal tumor cells at the beginning of the operation.

Intraperitoneal lavage fluid will be harvested and assessed for tumor cells at three different points of time:

(i) before gastrectomy and lymphadenectomy (ii) after gastrectomy and lymphadenectomy, directly before EIPL (iii) after EIPL

The trial will test the hypotheses that a) lymph node dissection causes a release of tumor cells in the abdominal cavity, and b) EIPL eliminates free peritoneal tumor cells.

  Eligibility

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

Inclusion Criteria:

  • Adenocarcinoma of the stomach or cardia (Siewert Type 2 or 3), treated in curative intent with a gastrectomy or subtotal gastrectomy, and D2 lymphadenectomy.
  • Adjuvant and neoadjuvant therapy do not constitute exclusion criteria
  • Written informed consent
  • Age ≥ 18 years

Exclusion Criteria:

  • Histologically proven peritoneal carcinomatosis (biopsies of macroscopically suspicious findings must be taken at the beginning of the operation and be analyzed immediately by fresh frozen section)
  • Histologically proven distant metastases
  • Other medical causes precluding EIPL (e.g. critical condition throughout the surgery with the need to terminate the operation as soon as possible)
  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: NCT01476553

Locations
Germany
University Hospital Mannheim, Department of Surgery
Mannheim, Germany, 68167
Sponsors and Collaborators
Universitätsmedizin Mannheim
Heidelberg University
Investigators
Principal Investigator: Ulrich Ronellenfitsch, MD University Hospital Mannheim, Department of Surgery
  More Information

Publications:

Responsible Party: Ulrich Ronellenfitsch, MD, Principal Investigator, University Hospital Mannheim
ClinicalTrials.gov Identifier: NCT01476553     History of Changes
Other Study ID Numbers: UMM-EIPL
Study First Received: November 11, 2011
Last Updated: March 21, 2013
Health Authority: Germany: Ethics Commission

Keywords provided by Universitätsmedizin Mannheim:
gastric cancer
extensive intraperitoneal lavage
EIPL
intraperitoneal tumor cells
peritoneal carcinomatosis

Additional relevant MeSH terms:
Adenocarcinoma
Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on July 26, 2014