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

Metastatic Colorectal Cancer Clinical Trial

— COPERNIC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05487248
• Other study ID #: IJB-COPERNIC-ODN-012
• Status: Recruiting
• Phase: N/A
• Start date: October 12, 2023
• Est. completion date: July 12, 2026

Study information

• Verified date: October 2023
• Source: Jules Bordet Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

• FoundationOne®Tracker for monitoring purpose

Time points for blood samples collection:

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

• Before treatment start (day 1)

• 2 weeks after treatment start (day 15)

• 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)

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

• Before treatment start (day 1)

• 3 weeks after treatment start (day 22)

• 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)

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 103
• Est. completion date: July 12, 2026
• Est. primary completion date: January 12, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Other:
• Blood Sample Collection
For subjects receiving treatments with a 2- or 4-weekly schedule, blood samples for ctDNA testing will be collected at the following timepoints: Before treatment start (day 1) 2 weeks after treatment start (day 15) 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) For subjects receiving treatments with a 3-weekly schedule, blood samples for ctDNA testing will be collected at the following timepoints: Before treatment start (day 1) 3 weeks after treatment start (day 22) 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)

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	UZ Antwerpen	Antwerpen
Belgium	CHIREC Delta	Brussels
Belgium	CHU Ambroise Pare	Mons
Belgium	Cliniques Universitaires Saint Luc	Woluwe-Saint-Lambert
France	Centre Georges François Leclerc	Dijon
France	Hopital Franco-Britannique - Fondation Cognacq-Jay	Levallois-Perret
France	Hopital privé Jean Mermoz	Lyon
France	Hopital St-Louis	Paris
France	CHU Poitiers	Poitiers
France	ICO	Saint-Herblain
France	ICANS Strasbourg	Strasbourg

Sponsors (2)

Lead Sponsor	Collaborator
Jules Bordet Institute	Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	prognostic value of ctDNA.	To confirm the prognostic value of ctDNA.	through study completion, an average of 1 year
Primary	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 F1LCDx and FoundationOne®Tracker and F1LCDx) that predict progressive disease as best radiological response with a high degree of specificity.	Day 15 or 22
Secondary	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 FoundationOne®Tracker) that predict progressive disease as best radiological response with a high degree of specificity.	Day 29 or 43
Secondary	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
Secondary	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
Secondary	CGP changes during treatment	To track CGP changes during treatment as assessed by F1LCDx.	Day 1 and 15 or D1 and D22