The Immunoscore as a Prognostic Marker for Patients With a Colorectal Cancer (IMMUCOL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2011 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01688232
First received: September 14, 2012
Last updated: March 28, 2013
Last verified: December 2011
  Purpose

Medical and Scientific Background: Colorectal cancers (CRC) are the leading cancers in both genders. This cancer is of prognostic severity. The prognosis of this cancer has not been significantly improved. The treatment of colonic cancer is primarily based on surgery. Adjuvant chemotherapy is proposed for metastatic cancers (stages III and IV). However nearly 30% of patients with localized cancer (stage II) will present a recurrence. Despite intense research efforts, no markers of sufficient prognostic value (independent of TNM) are available to identify this group of patients and justify intensified therapy. The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. We showed that the density of intratumor memory T cells (CD45RO) and cytotoxic T cells (CD8) in tumor regions (the core and the invasive margin) influenced the occurrence of early events of metastasis (tumor emboli) and was strongly associated with prognosis of patients with CRC (Pagès et al, NEJM-2005). This immune criterion was a better predictor of survival than the "gold standard" histoprognostic data of tumor invasion (T stage and N) and allowed to identify a group of patients at high risk of recurrence (*2). The availability of this immune criterion in clinical practice could improve the prognostic assessment of patients and better guide the therapeutic. A dedicated platform has been implemented in our hospital to speed up the transfer of this immune investigation into the clinic. The investigation takes into account the density of immune cell populations in tumor regions (the core and the invasive front of the tumor). This methodology has been validated for the markers CD45RO, CD3 and CD8 and leads to the creation of an immune score ("immunoscore" ranging from IO to I4). We validated the prognostic impact of the immunoscore in a retrospective series of 250 colorectal cancers. The main objective of this multicentric prospective clinical study is to assess in clinical practice the "immunoscore" and measure its prognostic value. The cohort study will include 400 patients with CRC stage I to IV (6 centers for inclusion; Paris-HEGP, Dijon, Bobigny-Avicenne, Besancon, Poitiers, Rouen). Two years of inclusion and a follow-up of 3 years for each patient will be performed (co-financing for data collection during the 4th and 5th year planned). For each patient, the pathologist of the center will send to the immunomonitoring platform of HEGP tissue sections from a paraffin block containing the tumor regions. The investigations will combine a step of immunostaining for CD3, CD8, and CD45RO (Ventana automate) markers, high-resolution scanning of the stained slides and quantification of digital images by an imaging module developed by our group from the program of Developer XD of Définiens company. The immunoscore will be calculated and the score will be correlated to the clinical data for the relapse and the survival. The secondary objective of this program is to evaluate the prognostic performance of the immune infiltrate on the biopsies performed for diagnostic purposes. This study will be conducted on patients of the cohort whose biopsies were performed in the same hospital than surgery and whose samples are available in pathology laboratories involved (representing 50% of cases). For the same patients will be conducted a genetic investigation of the tumor to assess the MSI status, the presence of a K-Ras and BRAF mutations. This investigation will be performed on tumor sections from the same tumor block selected for the immunohistochemical analyses. The sections will be processed by the Department of Biology, Hôpital Européen Georges Pompidou. The prognostic performance of the immune investigations performed on tumor sections and biopsies will be compared to that of genetic features of the tumor. Finally, a questionnaire will be sent every six months along the monitoring of the patients to obtain information concerning (i) the emergence of an immune disorder (such as allergy, autoimmunity, inflammatory process) and (ii) the psychological status of the patients. The potential impact of such parameters during the course of the disease on the prediction of the relapse and survival obtained with the immunoscore performed at the time of surgery will be evaluated. Expected results : This prospective study is an indispensable step for the clinical validation of the prognostic value of the immunoscore. The secondary objectives should help to precise the benefit of a concomitant analysis of the biopsy, the genetic features of the tumor. The questionnaire should help to identify the clinical parameters to track along the monitoring


Condition
Colorectal Cancer
Surgical Resection of the Colorectal Tumor

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Colorectal Cancer: a Prospective Multicentric Study of the in Situ Immune Infiltrate for the Identification of the Patients at High Risk of Relapse

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • relapse in relation with the immunoscore determined on a tumor section. [ Time Frame: evry 3 month during 3 years and every six months during the fourth year ] [ Designated as safety issue: No ]
    this primary outcome (relapse) will be correlated to the immunoscore determined in the primary tumor (eg. the density of immune cells in tumor regions)


Secondary Outcome Measures:
  • relapse in relation with the immunoscore on biopsies [ Time Frame: evry 3 month during 3 years and every six months during the fourth year ] [ Designated as safety issue: No ]
    this primary outcome (relapse) will be correlated to the immunoscore determined in biopsies performed for diagnosis purpose (eg. the density of immune cells in the biopsies specimens)

  • relapse in relation with the genetic features of the tumor [ Time Frame: evry 3 month during 3 years and every six months during the fourth year ] [ Designated as safety issue: No ]
    this primary outcome (relapse) will be correlated to the genetic features of the tumor (eg. MSI status, K-Ras and BRAF mutations). The prognostic performance of the genetic and immunologic analyses will be compared.

  • relapse in relation with the immunological events and psychological status of the patient during the monitoring [ Time Frame: every six months during 4 years ] [ Designated as safety issue: No ]
    a questionnaire will be sent every six months along the monitoring of the patients to obtain informations concerning (i) the emergence of an immune disorder and (ii) the psychological status of the patients. The potential impact of such parameters during the course of the disease on the prediction of the relapse and survival obtained with the immunoscore performed at the time of surgery will be evaluated. The questionnaire should help to identify the clinical parameters to track along the monitoring.


Biospecimen Retention:   Samples With DNA

The pathologist of each center will choose a tumor block containing the core of the tumor and the invasive margin. Three tissue sections of 4 microns of this tumor block will be cut and deposited on glass slides for the immunohistochemical analyses. Four tissue sections of 4 microns will be cut and deposited in a safe lock eppendorf tube for a DNA extraction. If biopsies for diagnostic purpose are available in the laboratory of pathology for the same patient, one tissue section of 4 microns of each biopsy will be cut and deposited on a glass slide


Estimated Enrollment: 400
Study Start Date: October 2012
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult patient with newly diagnosed colorectal cancer.

Criteria

Inclusion Criteria:

  • Adult patient with newly diagnosed colorectal cancer.
  • Patient with signed informed consent.
  • Follow up made by the clinical center for inclusion or by a medical team in relation with the center.

Exclusion Criteria:

  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: NCT01688232

Locations
France
Hopital de Besançon (CHU) Recruiting
Besançon, France, 25000
Contact: Olivier Adotevi, Professor    33 3 81 66 93 51 ext 33    olivier.adotevi@univ-fcomte.fr   
Contact: Christophe Borg    33 3 81 66 87 05 ext 33    christophe.borg@univ-fcomte.fr   
Hopital Avicenne (CHU) Recruiting
Bobigny, France, 93000
Contact: Philippe Wind, Professor    33 1 48 95 52 21 ext 33    philippe.wind@avc.aphp.fr   
Contact: Christine Lagorce, Doctor    33 1 48 95 56 07 ext 33    christine.lagorce@avc.aphp.fr   
Hopital de Dijon (CHU) Recruiting
Dijon, France, 21000
Contact: Laurent Martin, Professor    33 3 80 39 33 46 ext 33    laurent.Martin@u-bourgogne.fr   
Contact: Come Lepage    33 3 80 39 33 40 ext 33    come.lepage@u-bourgogne.fr   
Hopital Europeen Georges Pompidou (HEGP) Recruiting
Paris, France, 75015
Contact: Anne Berger, Professor    331 56 09 35 30 ext 33    anne.berger@egp.aphp.fr   
Contact: Franck Pagès, Professor    33 1 56 09 39 46 ext 33    franck.pages@egp.aphp.fr   
Hopital de Poitiers (CHU) Not yet recruiting
Poitiers, France, 86000
Contact: David Tougeron, Doctor    33 5.49.44.37.51 ext 33    david.tougeron@chu-poitiers.fr   
Hopital Charles Nicolle(CHU) Recruiting
Rouen, France, 76000
Contact: Jean-Baptiste Latouche, Doctor       Jean-Baptiste.Latouche@chu-rouen.fr   
Contact: Florence Le Pessot, doctor    33 2 32 88 82 12 ext 33    Florence.Le-Pessot@chu-rouen.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
Principal Investigator: Franck Pagès, Professor (MD-PHD) AP-HP; Paris Descartes University
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01688232     History of Changes
Other Study ID Numbers: NI11033
Study First Received: September 14, 2012
Last Updated: March 28, 2013
Health Authority: France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:
colorectal cancer
tumor resection
immunoscore
lymphocytic density
CD3
CD8
CD45RO
biopsy
genetic feature of the tumor
relapse
immunohistochemistry
image analysis software

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 29, 2014