ctDNA in CRC Patients Undergoing Curative-intent Surgery for Liver Metastases (CLIMES)

Circulating Tumor DNA in Patients With Colorectal Cancer Undergoing Curative-intent Surgery for Liver Metastases: Prospective, Multicenter, GERCOR Cohort

This is a prospective multicenter cohort study, was designed to explore the prognostic value of ctDNA as a biomarker of disease response and recurrence or death in patients undergoing curative-intent surgical resection of Colorectal cancer liver metastasis.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer; Circulating Tumor DNA

Detailed Description

Blood collection times according to specific clinical situations:

• Standard approach
• Combined surgery
• Reverse strategy
• Two-stage hepatectomy

• Study Type: Observational
• Enrollment (Estimated): 232

Contacts and Locations

• Study Contact: Name: Maximiliano GELLI, MD; Phone Number: +33(0)1 40 29 85 00; Email: maximiliano.gelli@gustaveroussy.fr
• Study Contact Backup: Name: Marie Line GARCIA, MD; Phone Number: +33(0)1 40 29 85 00; Email: marie-line.garcia-larnicol@gercor.com.fr

Study Locations

• France
  • Besançon, France
    • Not yet recruiting
    • CHU Jean Minjoz
    • Contact: Christophe BORG, MD
  • Bordeaux, France
    • Not yet recruiting
    • Institut Bergonié
    • Contact: Grégoire DESOLNEUX, MD
  • Lille, France
    • Recruiting
    • CHU Lille - Hopital Huriez
    • Contact: Stéphanie TRUANT, MD
  • Lyon, France
    • Not yet recruiting
    • Centre Léon Bérard
    • Contact: Aurélien DUPRE, MD
  • Paris, France
    • Not yet recruiting
    • Hôpital Pitié Salpêtrière
    • Contact: Claire GOUMARD, MD
  • Paris, France
    • Not yet recruiting
    • Hôpital Saint Antoine
    • Contact: François PAYE, MD
  • Paris, France
    • Not yet recruiting
    • Institut Mutualiste Montsouris
    • Contact: David MLAKA, MD
  • Paris, France
    • Not yet recruiting
    • Hopital Cochin
    • Contact: David FUKS, MD
  • Paris, France
    • Not yet recruiting
    • Hopital Bichat Claude Bernard
    • Contact: Gaël GOUJON, MD
  • Pessac, France
    • Not yet recruiting
    • Hôpital Haut Lévêque
    • Contact: Denis SMITH, MD
  • Poitiers, France
    • Recruiting
    • CHU de Poitiers
    • Contact: Camille EVRARD, MD
  • Rouen, France
    • Not yet recruiting
    • CHU Rouen
    • Contact: Frédéric FIORE, MD
  • Strasbourg, France
    • Not yet recruiting
    • CHU Strasbourg
    • Contact: Pietro ADDEO, MD
  • Tours, France
    • Not yet recruiting
    • CHRU Tours
    • Contact: Petru BUCUR, MD
  • Villejuif, France
    • Not yet recruiting
    • Institut Gustave Roussy
    • Contact: Maximiliano GELLI, MD
  • Villejuif, France
    • Not yet recruiting
    • Hopital Paul Brousse
    • Contact: René ADAM, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Active file in oncology department

Description

Inclusion criteria

The patient will be included if:

1. Has signed informed consent form and is willing to comply with all study procedures and availability for the study duration,
2. Is ≥ 18 years of age,
3. Has histologically confirmed colorectal adenocarcinoma,
4. Has resected primary tumor or is eligible to primary tumor and CRLM (in case of synchronous metastases) resection within 6 months prior to study inclusion,
5. Has isolated CRLM that is deemed resectable or potentially resectable (extrahepatic metastases excluded, except infracentimetric non-specific lung lesions with largest diameter <1 cm and maximal number of ≤3) as judged by a multidisciplinary team meeting (based on CT scans of chest, abdomen, and pelvis [or MRI if CT not possible]),
6. Is eligible to surgical procedure,
7. Is fit for the chemotherapy-surgery combination treatment,
8. Is registered in a national health care system (Protection Universelle Maladie [PUMa] included).

Exclusion criteria

The patient will be excluded if:

1. Has definitively unresectable CLRM,
2. Had more than 9 pre-operative cycles of chemotherapy for treatment of metastatic disease planned at inclusion,
3. Has not resected primary rectal tumor (low and middle),
4. Has history of another primary cancer within the last 5 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix,
5. Has no more than two surgical procedures planned for complete resection of primary tumor and/or liver metastases,
6. Has deficient mismatch repair (dMMR)/ microsatellite instability (MSI) tumors treated with immunotherapy,
7. Blood samples cannot be collected if surgical procedure,
8. Is pregnant or breastfeeding,
9. Cannot be followed-up due to geographical, social, or psychic conditions,
10. Has medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol,
11. Is under guardianship, curatorship, or under the protection of justice.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS) in patients who undergo curative-intent resection of colorectal liver metastasis (CRLM)	DFS is defined as the time from complete surgical resection (following first surgery if one-stage surgery or second surgery if two-stage strategy) to first documented event (relapse or death, whichever occurred first), or until last contact if no event occurs.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of event-free survival (EFS) in patients who undergo curative-intent resection of CRLM.	EFS is defined as time between inclusion until the occurrence of an event: disease progression, relapse, disease progression, or death from any reason.	Up to 4 years
Overall survival (OS) n patients who undergo curative-intent resection of CRLM.	OS is defined as the time between inclusion and death. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.	Up to 4 years
Time to surgical failure (TSF) in patients who undergo curative-intent resection of CRLM.	TFS is defined as the time from initial surgery until the first unresectable recurrence or death from any cause or the date of the last follow-up, at which point data are censored.	Up to 4 years
Prognostic value of ctDNA	Prognostic value of ctDNA: post-operative ctDNA detection,; relative change in ctDNA level after curative resection of CRLM,; ctDNA in different subgroups of patients classified according to the type of surgical strategy (standard approach, combined surgery, reverse strategy, two-staged hepatectomy),	Up to 4 years
Prognostic factor(s) for disease recurrence and survival.	Prognostic factor(s) for disease recurrence and survival in patients who undergo curative-intent resection of CRLM.	Up to 4 years
Association between ctDNA and clinical features.	To identify the clinical, biological, and pathological factors associated with the ctDNA level.	Up to 4 years

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Principal Investigator: Maximiliano GELLI, MD, Department of Digestive Surgery, Gustave Roussy Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): September 25, 2025
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CLIMES G-118 CIRCULATE-4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No