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Personalizing Colorectal Cancer Medicine (ImmuCol2) (ImmuCol2)

11. oktober 2021 oppdatert av: Assistance Publique - Hôpitaux de Paris

Personalizing Colorectal Cancer Medicine: an Integrative Approach for the Identification of Prognostic Parameter Combinations at the Time of Surgery and During the Follow-up

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.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Detaljert beskrivelse

The project aims:

(i) to combine at time of diagnosis the immunoscore with parameters related to the patient, its tumor and the associated microenvironment (ii) to detect events occurring during the follow up period that could modify the initial prognosis and lead to a repositioning of the patient, to move towards a dynamic personalized medicine.

(iii) to explore the Theranostic aspect of the parameters monitored at the time of diagnosis for patients with colonic cancers treated with adjuvant chemotherapy.

To this end we will investigate:

  • Tumor's features:

    - We will determine the microsatellite instability status and search for mutations of 46 genes (ABL1, AKT1, ALK, APC, ATM, BRAF, CCDH1, CDKN2A, CSF1R, CTNNB, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, NOTCH1, NPM1, NRAS, PDGFRA, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, STK11, TP53, VHL) by next generation sequencing (NGS).

  • Tumor immune microenvironment features:

    - 24 immune related genes, 24 miRNA and co-inihibitory molecules (PD1, PD1-L, LAG-3, TIM3, CTLA-4) will be explored on tumor samples.

  • Systemic disorders:

    • Autoimmunity, allergy or inflammatory diseases will be sought with a dedicated questionnaire filled out by the patient and a serum examination for the screening of immune disorders at the time of diagnosis and during the survey.
    • The nutritional status (% of weight loss) and the deficiencies in vitamins, folic acid, trace elements and thyroid hormones that synergise with immune cells will be determined at the time of diagnosis.

  • Psychological status:

    - The impact of the psychological profile of the patient will be investigated with a dedicated questionnaire, given at the time of diagnosis and every six months.

  • Data mining to achieve a dynamic personalized medicine:

The integration and statistical analysis of heterogeneous data types (clinical and different experimental data) will be performed using with tranSMART, an open source platform and with bioinformatic tools (TMEdb, ClueGO, CluePedia, Genesis) developed by participant teams.

Studietype

Observasjonsmessig

Registrering (Faktiske)

220

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Frankrike
      • Besançon, Frankrike, 25000
        • Hopital de Besançon (CHU)
      • Bobigny, Frankrike, 93000
        • Hôpital Avicenne
      • Bordeaux, Frankrike, 33000
        • CHU de Bordeaux
      • Bordeaux, Frankrike, 33000
        • Institut Bergonié Bordeaux
      • Clichy, Frankrike, 92110
        • Hopital Beaujon
      • Dijon, Frankrike, 21000
        • Hopital de Dijon (CHU)
      • Paris, Frankrike, 75015
        • Hôpital Européen Georges Pompidou (HEGP)
      • Poitiers, Frankrike, 86000
        • Hopital de Poitiers (CHU)
      • Rouen, Frankrike, 76000
        • Hopital Charles Nicolle (CHU)

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

Adult patient with newly diagnosed colon cancer.

Beskrivelse

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Adjuvant treatment (chemotherapy) started at the time of inclusion

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Relapse in relation with the immunoscore determined on a tumor section and criteria defined in the monitoring of patients
Tidsramme: 3 years
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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Relapse in relation with the immune component cancers beyond immunoscore
Tidsramme: Every 3 months during 2 years and every 6 months during the third year
The primary outcome (relapse) will be correlated to the expression of immune molecules associated with activation or inhibition of T lymphocyte and by in situ analysis of the expression level of immune genes. A comparison of the prognostic performance of these parameters will be performed. These parameters will then be analyzed in combination with immunoscore to determine the optimal combination of immune parameters with prognostic and theranostic target.
Every 3 months during 2 years and every 6 months during the third year
Relapse in relation with the immunoscore on biopsies
Tidsramme: Every 3 months during 2 years and every 6 months during the third year
The primary outcome (relapse) will be correlated to the immunoscore and expression of immune genes determined on biopsies performed for diagnosis purpose
Every 3 months during 2 years and every 6 months during the third year

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Assistance Publique - Hôpitaux de Paris

Samarbeidspartnere

Ministry of Health, France

Publikasjoner og nyttige lenker

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Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

11. mars 2015

Primær fullføring (Forventet)

31. desember 2021

Studiet fullført (Forventet)

31. desember 2021

Datoer for studieregistrering

Først innsendt

20. oktober 2014

Først innsendt som oppfylte QC-kriteriene

22. oktober 2014

Først lagt ut (Anslag)

24. oktober 2014

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

12. oktober 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

11. oktober 2021

Sist bekreftet

1. oktober 2021

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • NI13017

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