Personalizing Colorectal Cancer Medicine (ImmuCol2)

NCT02274753 | Unknown

• 1 other identifier: NI13017
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 9

Brief Summary

Colorectal cancers are the leading cancers for both sexes combined. They represent 15-20% of all cancers. This cancer has a severe prognosis, the survival rate at 5 years is around 55% and in France it is estimated, all colorectal cancers are responsible for an annual mortality of 15,000 patients. The prognosis of colon cancer knows no significant improvement. The treatment of colon cancer is surgical. It is intended for removal of colonic segment bearing the tumor with margins of healthy colon. The therapeutic attitude following the surgery is essentially driven by histopathology of the tumor. Adjuvant chemotherapy for all patients with localized stage II provides no benefit because the effectiveness of chemotherapy is limited and vulnerable to systemic toxicity. However, nearly 30% of patients with stage II disease will have a recurrence / metastasis. These patients could benefit from adjuvant chemotherapy. Intense research efforts have been made to identify markers predictive of relapse. Over thirty biological markers (eg. Mutations, deletions, chromosomal instability, ...) were highlighted. None of them has so far sufficient prognostic value (independent of TNM) to justify routine application in clinical practice in order to adapt the treatment of patients. The identification of new prognostic markers is a major issue for colorectal cancer. We showed that the intratumoral density memory T lymphocytes (CD45RO) and cytotoxic (CD8) strongly influenced the clinical outcome of patients. We have developed and validated a "immunoscore" technique intratumoral immune quantification and creates a platform to facilitate the clinical immuno transfer. We are currently conducting a large international retrospective study (22 centers,\> 9000 patients) with promotion of cancer immunotherapy Company (SITC) to validate the method "immunoscore." At the same time, we are conducting a prospective multicenter study "ImmuCol" (National PHRC) to validate the prognostic value of "immunoscore" in colorectal cancer stage I-IV. The goal of inclusion has been achieved, as 420 patients were included for 18 months. Clinical follow-up will be 3 years after surgery. The program ImmuCol2 research takes advantage of the ImmuCol study to extend the investigation beyond the immunoscore to define the combination of interest, prognostic and theranostic parameters at diagnosis and during the clinical course patients with an objective of personalized medicine.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Relapse in relation with the immunoscore determined on a tumor section and criteria defined in the monitoring of patients

  This primary outcome (relapse) will be correlated to the immunoscore and several criteria (dysimmune systemic criteria, malnutrition, vitamin deficiencies in micronutrients, psychological criteria) in order to evaluate their pronostic impact. The measure is a composite outcome.

  3 years

Secondary Outcomes (2)

• Relapse in relation with the immune component cancers beyond immunoscore

  Every 3 months during 2 years and every 6 months during the third year

• Relapse in relation with the immunoscore on biopsies

  Every 3 months during 2 years and every 6 months during the third year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patient with newly diagnosed colon cancer.

You may qualify if:

• Adult patient with newly diagnosed colon cancer
• Patient with signed informed consent
• Patient follow-up during the first three years made in the recruiting center

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator

Study Sites (9)

Hopital de Besançon (CHU)

Besançon, 25000, France

Location

Hopital Avicenne

Bobigny, 93000, France

Location

CHU de Bordeaux

Bordeaux, 33000, France

Location

Institut Bergonié Bordeaux

Bordeaux, 33000, France

Location

Hopital Beaujon

Clichy, 92110, France

Location

Hopital de Dijon (CHU)

Dijon, 21000, France

Location

Hopital Europeen Georges Pompidou (HEGP)

Paris, 75015, France

Location

Hopital de Poitiers (CHU)

Poitiers, 86000, France

Location

Hopital Charles Nicolle (CHU)

Rouen, 76000, France

Location

Related Publications (14)

• Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002 Nov;3(11):991-8. doi: 10.1038/ni1102-991.

  PMID: 12407406 BACKGROUND

• Saltz LB, Kelsen DP. Adjuvant treatment of colorectal cancer. Annu Rev Med. 1997;48:191-202. doi: 10.1146/annurev.med.48.1.191.

  PMID: 9046955 BACKGROUND

• Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005 Dec 22;353(25):2654-66. doi: 10.1056/NEJMoa051424.

  PMID: 16371631 BACKGROUND

• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006 Sep 29;313(5795):1960-4. doi: 10.1126/science.1129139.

  PMID: 17008531 BACKGROUND

• Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Marliot F, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, Fridman WH, Galon J. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009 Dec 10;27(35):5944-51. doi: 10.1200/JCO.2008.19.6147. Epub 2009 Oct 26.

  PMID: 19858404 BACKGROUND

• Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011 Feb 20;29(6):610-8. doi: 10.1200/JCO.2010.30.5425. Epub 2011 Jan 18.

  PMID: 21245428 BACKGROUND

• Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D'Arrigo C, Vidal-Vanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pages F. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours. J Pathol. 2014 Jan;232(2):199-209. doi: 10.1002/path.4287.

  PMID: 24122236 BACKGROUND

• Myron Kauffman H, McBride MA, Cherikh WS, Spain PC, Marks WH, Roza AM. Transplant tumor registry: donor related malignancies. Transplantation. 2002 Aug 15;74(3):358-62. doi: 10.1097/00007890-200208150-00011.

  PMID: 12177614 BACKGROUND

• Dalerba P, Maccalli C, Casati C, Castelli C, Parmiani G. Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hematol. 2003 Apr;46(1):33-57. doi: 10.1016/s1040-8428(02)00159-2.

  PMID: 12672517 BACKGROUND

• Jass JR. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol. 1986 Jun;39(6):585-9. doi: 10.1136/jcp.39.6.585.

  PMID: 3722412 BACKGROUND

• Phillips SM, Banerjea A, Feakins R, Li SR, Bustin SA, Dorudi S. Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic. Br J Surg. 2004 Apr;91(4):469-75. doi: 10.1002/bjs.4472.

  PMID: 15048750 BACKGROUND

• Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010 Feb 25;29(8):1093-102. doi: 10.1038/onc.2009.416. Epub 2009 Nov 30.

  PMID: 19946335 BACKGROUND

• Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012 Mar 15;12(4):298-306. doi: 10.1038/nrc3245.

  PMID: 22419253 BACKGROUND

• Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, Bruneval P, Fridman WH, Becker C, Pages F, Speicher MR, Trajanoski Z, Galon J. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013 Oct 17;39(4):782-95. doi: 10.1016/j.immuni.2013.10.003.

  PMID: 24138885 BACKGROUND

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. Seven tissues sections (five of 4 microns and two of 20 microns) of this tumor bmock will be cut and deposited on glass slides for the immunohistochemical and tumor genetic analysis. If biopsies for diagnostic purpose are available in the laboratory of pathology for the same patient, two tissue sections of 4 microns of each biopsy will be cut and deposited on a glass slide. Two tubes of blood (5 ml tube without anticoagulant) and a 10 ml tube with EDTA will be taken in consultation or hospitalization before the first chemotherapy and at 1 year, 2 years and 3 years. These samples will be used for gene expression analysis and in the search for biological signs of autoimmunity.

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Franck Pages, Professor (MD-PHD)

  AP-HP; Paris Descartes University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 24, 2014
• Study Start: March 11, 2015
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: October 12, 2021

Record last verified: 2021-10

Locations

FR (9)