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

• ClinicalTrials.gov Identifier: NCT05487248
• Recruitment Status: Recruiting
• First Posted: August 4, 2022
• Last Update Posted: May 9, 2024
• Sponsor: Jules Bordet Institute
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Jules Bordet Institute

Tracking Information

• First Submitted Date: May 27, 2022
• First Posted Date: August 4, 2022
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: October 12, 2023
• Estimated Primary Completion Date: January 12, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2022)

Optimal timepoint and cut-off value for early on-treatment ctDNA changes [ Time Frame: Day 15 or 22 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2022)

• optimal timepoint and cut-off value for on-treatment ctDNA changes at 4 or 6 weeks [ Time Frame: Day 29 or 43 ]
  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.
• rapid turnaround time of ctDNA testing based on F1LCDx [ Time Frame: through study completion, an average of 1 year ]
  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.
• tumour heterogeneity [ Time Frame: Day 1 ]
  To evaluate tumour heterogeneity before treatment start as assessed by F1CDx in the tumour tissue and F1LCDx in the whole blood.
• CGP changes during treatment [ Time Frame: Day 1 and 15 or D1 and D22 ]
  To track CGP changes during treatment as assessed by F1LCDx.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 2, 2022)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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

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
• 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).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Unresectable Locally Advanced Colorectal Cancer
• Metastatic Colorectal Cancer
• Candidate for Third-line or Subsequent Lines of Therapy

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)

Study Arms

Experimental: Unresectable locally advanced or metastatic colorectal cancer patients

● Samples collection:

• Collection of blood samples 6 x 9 ml at day 1
• Collection of blood samples 4 x 9 ml at day 15 and day 29
• Collection of blood samples 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)

Intervention: Other: Blood Sample Collection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 2, 2022): 103
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 12, 2026
• Estimated Primary Completion Date: January 12, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Belgium, France

Administrative Information

• NCT Number: NCT05487248
• Other Study ID Numbers: IJB-COPERNIC-ODN-012
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jules Bordet Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Jules Bordet Institute
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche
• Investigators: Not Provided
• PRS Account: Jules Bordet Institute
• Verification Date: October 2023