A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients (COPERNIC)

COPERNIC is an international, multicentre, single-arm study. Chemo-refractory mCRC subjects who meet all eligibility criteria will be treated with standard systemic chemotherapy (the decision about the treatment regimen being made by the treating physician) and undergo tumour assessment by standard imaging (either CT scan or MRI scan) at baseline and every 8 or 12 weeks until evidence of tumour progression. Response to treatment will be assessed by the local investigators according to the RECIST criteria version 1.1. Blinded, independent central review of the imaging scan will be carried out, this having no impact on treatment decisions thatwhich will remain the prerogative of the treating physician.

Serial blood samples from study subjects will be collected at pre-defined time points for ctDNA testing. Also, archived tumour tissue from each subject will be collected. Prospective and retrospective ctDNA analyses on blood samples will be carried out, and dynamics of ctDNA will be correlated with treatment outcomes prognosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer; Unresectable Locally Advanced Colorectal Cancer; Candidate for Third-line or Subsequent Lines of Therapy
• Intervention / Treatment: Other: Blood Sample Collection

Detailed Description

COPERNIC is an international, multicentre, single-arm study. Chemo-refractory mCRC subjects who meet all eligibility criteria will be treated with standard systemic chemotherapy (the decision about the treatment regimen being made by the treating physician) and undergo tumour assessment by standard imaging (either CT scan or MRI scan) at baseline and every 8 or 12 weeks until evidence of tumour progression. Response to treatment will be assessed by the local investigators according to the RECIST criteria version 1.1. Blinded, independent central review of the imaging scan will be carried out, this having no impact on treatment decisions which will remain the prerogative of the treating physician.

Serial blood samples from study subjects will be collected at pre-defined time points for ctDNA testing. Also, archived tumour tissue from each subject will be collected. Prospective and retrospective ctDNA analyses on blood samples will be carried out, and dynamics of ctDNA will be correlated with prognosis.

Two ctDNA assays will be used in this study:

• FoundationOne Liquid CDx (F1LCDx) for comprehensive genomic profile (CGP) assessment
• F1Monitor for monitoring purpose

For subjects receiving treatments with a 2- or 4-weekly schedule, blood and plasma samples for ctDNA testing will be collected at the following timepoints:

Blood :

• Before treatment start (day 1)
• 2 weeks after treatment start (day 15)

Plasma :

• Before the treatment start (day 1)
• 4 weeks after treatment start (day 29)
• 8 or 12 weeks after treatment start and every 8 or 12 weeks thereafter (i.e. at the same time of each imaging tumour assessment) until evidence of progressive disease by RECIST 1.1

For subjects receiving treatments with a 3-weekly schedule, blood and plasma samples for ctDNA testing will be collected at the following timepoints:

Blood :

• Before treatment start (day 1)
• 3 weeks after treatment start (day 22)

Plasma :

• Before treatment start (day 1)
• 6 weeks after treatment start (day 43)
• 8 or 12 weeks after treatment start and every 8 or 12 weeks thereafter (i.e. at the same time of each imaging tumour assessment) until evidence of progressive disease by RECIST 1.1

ctDNA analyses will be done in a centralised laboratory (Foundation Medicine Inc). Full report of the ctDNA analysis will be provided to the study team to allow correlation with clinical data and exploratory analyses. The results of the ctDNA analysis will not be communicated to the treating physician (with the only exception of the analysis by F1CDx on tumour tissue at screening) and therefore will not have any impact on treatment decision (i.e., all study subjects will be treated according to standard practice).

• Study Type: Interventional
• Enrollment (Estimated): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Antwerp, Belgium
    • UZ Antwerpen
  • Brussels, Belgium
    • Chirec Delta
  • Mons, Belgium, 7000
    • CHU Ambroise Pare
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Cliniques Universitaires Saint Luc
• France
  • Dijon, France
    • Centre Georges François Leclerc
  • Levallois-Perret, France, 92300
    • Hopital Franco-Britannique - Fondation Cognacq-Jay
  • Lyon, France
    • Hopital Prive Jean Mermoz
  • Paris, France
    • Hopital St-Louis
  • Poitiers, France
    • CHU Poitiers
  • Saint-Herblain, France
    • ICO Saint-Herblain
  • Strasbourg, France
    • ICANS Strasbourg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Male or female
3. ECOG performance status ≤2
4. Must have histologically or cytologically verified colorectal cancer adenocarcinoma
5. Inoperable locally advanced or metastatic disease
6. Presence of measurable disease (by RECIST criteria version 1.1) on baseline CT scan of the thorax/abdomen/pelvis or CT scan of the thorax and MRI of the abdomen/pelvis
7. At least two prior systemic treatments for advanced/metastatic colorectal cancer including oxaliplatin and irinotecan-based therapy (adjuvant or neoadjuvant systemic chemotherapy will be considered if tumour progression was documented within 6 month of the last chemotherapy dose)
8. Candidate for standard third-line or subsequent lines of therapy as per decision of the treating physician
9. Life expectancy of at least 3 months
10. Women of childbearing potential must have a negative serum pregnancy test done within 28 days prior to enrolment.
11. Effective contraception is in place for women of childbearing potential.
12. Completion of all necessary screening procedures within 28 days prior to enrolment.
13. Availability of archived tumour tissue

14. Signed Informed Consent form (ICF) obtained prior to any study related procedure.

    Inclusion criterion applicable to FRANCE only

15. Affiliated to the French Social Security System

Exclusion Criteria:

1. Tumours other than colorectal cancer
2. Histologies other than adenocarcinoma
3. Any baseline medical condition that would contraindicate the use of systemic chemotherapy or may preclude the regular administration of the same
4. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
5. Other invasive malignancy within 3 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
6. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.

7. Pregnant and/ or lactating women

   Exclusion criterion applicable to FRANCE only

8. Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Unresectable locally advanced or metastatic colorectal cancer patients; ● Samples collection: Blood samples 2 x 9 ml at day 1 2 x 9ml at day 15 Plasma samples 2 x 9 ml at day 1 4 x 9 ml at day 29 4 x 9 ml at week 8 or 12 and every 8 or 12 weeks thereafter (+/- 7 days) until evidence of progressive disease by RECIST 1.1 (according to local assessment)

Other: Blood Sample Collection; For subjects receiving treatments with a 2- or 4-weekly schedule, samples for ctDNA testing will be collected at the following timepoints: Blood : Before treatment start (day 1); 2 weeks after treatment start (day 15) Plasma : Before the treatment start (day 1); 4 weeks after treatment start (day 29); 8 or 12 weeks after treatment start and every 8 or 12 weeks thereafter (i.e. at the same time of each imaging tumour assessment) until evidence of progressive disease by RECIST 1.1 For subjects receiving treatments with a 3-weekly schedule, samples for ctDNA testing will be collected at the following timepoints: Blood : Before treatment start (day 1); 3 weeks after treatment start (day 22) Plasma : Before treatment start (day 1); 6 weeks after treatment start (day 43); 8 or 12 weeks after treatment start and every 8 or 12 weeks thereafter (i.e. at the same time of each imaging tumour assessment) until evidence of progressive disease by RECIST 1.1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal timepoint and cut-off value for early on-treatment ctDNA changes	To select the optimal timepoint and cut-off value for early on-treatment ctDNA changes (as assessed by F1Monitor) that predict progressive disease as best radiological response with a high degree of specificity.	at 2 or 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rapid turnaround time of ctDNA testing based on F1LCDx	To demonstrate rapid turnaround time of ctDNA testing based on F1LCDx and identify technical or logistical challenges to the implementation of an on-treatment ctDNA-driven treatment approach in a follow-on study.	through study completion, an average of 1 year
tumour heterogeneity	To evaluate tumour heterogeneity before treatment start as assessed by F1CDx in the tumour tissue and F1LCDx in the whole blood.	Day 1
CGP changes during treatment	To track CGP changes during treatment as assessed by F1LCDx.	Day 1 and 15 or D1 and D22
optimal timepoint and cut-off value for on-treatment ctDNA changes at 4 or 6 weeks	To select the optimal timepoint and cut-off value for on-treatment ctDNA changes at 4 or 6 weeks (as assessed by F1Monitor) that predict progressive disease as best radiological response with a high degree of specificity.	Day 29 or 43

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
exploratory genomics and radiomics profiles associated with progresdsive disease as best radiological response	To characterize the positive predictive value of baseline genomic and radiomic profiles for tumour progression at the first radiological assessment	through study completion, an average of 1 year
prognostic value of ctDNA.	To confirm the prognostic value of ctDNA.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Jules Bordet Institute
• Collaborators: Hoffmann-La Roche

Publications and helpful links

General Publications

• Assaf I, Bregni G, Anthoine G, Aparicio T, Artru P, Abdelghani MB, Buyse M, Chibaudel B, Coart E, Diaz M, Evrard C, Geboes K, Ghiringhelli F, Puleo F, Raimbourg J, Vandamme T, Van den Eynde M, Hendlisz A, Sclafani F. Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients. Clin Colorectal Cancer. 2025 Mar;24(1):101-105. doi: 10.1016/j.clcc.2024.08.004. Epub 2024 Sep 3.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 12, 2026

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: IJB-COPERNIC-ODN-012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No