Clinical trial NCT05487248: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients
Official title: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Unresectable Locally Advanced Colorectal Cancer
Metastatic Colorectal Cancer
Candidate for Third-line or Subsequent Lines of Therapy
Keywords: colorectal cancer
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2022-08-04
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Optimal timepoint and cut-off value for early on-treatment ctDNA changes
timeFrame: at 2 or 3 weeks
Secondary outcomes:
measure: optimal timepoint and cut-off value for on-treatment ctDNA changes at 4 or 6 weeks
timeFrame: Day 29 or 43
measure: rapid turnaround time of ctDNA testing based on F1LCDx
timeFrame: through study completion, an average of 1 year
measure: tumour heterogeneity
timeFrame: Day 1
measure: CGP changes during treatment
timeFrame: Day 1 and 15 or D1 and D22
Other outcomes:
measure: exploratory genomics and radiomics profiles associated with progresdsive disease as best radiological response
timeFrame: through study completion, an average of 1 year
measure: prognostic value of ctDNA.
timeFrame: through study completion, an average of 1 year
Locations:
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Brussels
country: Belgium
facility: CHIREC Delta
city: Mons
country: Belgium
facility: CHU Ambroise Pare
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Levallois-Perret
country: France
facility: Hopital Franco-Britannique - Fondation Cognacq-Jay
city: Lyon
country: France
facility: Hopital privé Jean Mermoz
city: Paris
country: France
facility: Hopital St-Louis
city: Poitiers
country: France
facility: CHU Poitiers
city: Saint-Herblain
country: France
facility: ICO Saint-Herblain
city: Strasbourg
country: France
facility: ICANS Strasbourg
Study officials:
References: