Personalizing chemotherapy selection after surgery for patients with stage III colorectal cancer using a blood test

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

National funding (PHRC)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

ctDNA-negative cohort: The primary objective is to evaluate the non-inferiority of 6-month capecitabine alone (CAPE; de-escalation strategy) compared to 3-month capecitabine + oxaliplatin (CAPOX; standard therapy) in terms of 3-year disease-free survival (DFS) as adjuvant chemotherapy (ACT) protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-negative.

ctDNA-positive cohort: The primary objective is to evaluate the superiority of 6-month FOLFIRINOX (escalation strategy) compared to 6-month FOLFOX (standard therapy) in terms of 3-year DFS as an ACT protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-positive.

Secondary objectives 4

1. Efficacy objectives: To compare between treatment arms: Disease Free Survival (DFS), Overall Survival (OS), Time to Recurrence (TTR)
2. Safety objectives: To evaluate safety and tolerability of the study treatments (NCI-CTCAE version 6.0). To evaluate whether de-escalation chemotherapy (6-month CAPE) decreases neurotoxicity.
3. Exploratory objectives: To evaluate patient’s quality of life (QoL) o To evaluate if ctDNA testing allows for a better estimation of prognosis in patients with stage III colorectal cancer compared to the classical prognostic estimation. To identify biological factors predictive of DFS, TTR and OS, To assess the ctDNA status (negative versus positive) during treatment and follow-up (at 3, 6, 9, 12, 18, 24, 30, 36 months) after initiation of adjuvant chemotherapy, To correlate the ctDNA status with survival
4. Ancillary studies: To evaluate several ctDNA detection techniques (methylation, sequencing…)

Conditions and MedDRA coding

Stage III colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
2. Age ≥18 years and <80 years (for patients aged >70 years: G8 geriatric questionnaire score>14)
3. Histologically confirmed stage III pMMR/MSS colon and high rectum adenocarcinoma (T, N1 or N2, M0) excluding medium and low rectal cancers (≥12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery are still eligible), without gross or microscopic evidence of residual disease after surgery with curative intent.
4. No metastatic disease on CT-Scan and/or liver MRI done within 2 months before inclusion
5. Inclusion planned between 10 days to 6 weeks after surgery
6. ECOG performance status 0-1 (fit to receive FOLFIRINOX therapy)
7. No prior chemotherapy for CRC
8. No prior abdominal or pelvic irradiation for CRC
9. Adequate hematological function: neutrophils ≥1,500 /mm3, platelet count ≥100,000/mm3, hemoglobin ≥9 g/dL (5,6 mmol/L)
10. Total bilirubin ≤1.5 x ULN (upper limit of normal)
11. ASAT and ALAT ≤2.5 x ULN
12. Alkaline phosphatase ≤2.5 x ULN
13. Serum creatinine ≤120 μmol/L or creatinine clearance ≥50 mL/min according to Modification of Diet in Renal Disease (MDRD) formulae
14. Tumor tissue available at baseline
15. Women of childbearing potential must have negative serum pregnancy test done within 7 days before the start of study treatment
16. Men and women of childbearing potential must agree to use adequate contraception methods for the duration of study treatment and for 6 months after treatment discontinuation
17. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures
18. Patient must be affiliated to a social security system (or equivalent) or according to local regulatory requirements

Exclusion criteria 13

1. Peripheral neuropathy grade ≥1
2. Patients who have received neo-adjuvant treatment.
3. Comorbidity influencing the 3-year patients’ survival including clinically relevant cardiovascular disease, such as Ischemic myocardial infarction in the last year and/or unstable ischemic cardiopathy
4. Contra-indication to chemotherapy (inadequate bone marrow, hepatic, renal functions, hypersensitivity to one of the treatments or any of the excipients)
5. Patient must not have received bone marrow transplant
6. Patient must not have received blood transfusion within 3 months before inclusion
7. Participation in another therapeutic trial
8. Partial or complete dihydropyrimidine deshydrogenase (DPD) deficiency.
9. MSI/dMMR tumors
10. Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years.
11. Pregnant or breastfeeding women.
12. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial social or psychological reasons
13. Persons deprived of their liberty or under protective custody or guardianship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The 3-year Disease-Free Survival (DFS) rate; DFS will be defined as time from randomization to first event (i.e, either a first recurrence local or metastatic (radiological or clinical), second colorectal cancer, or death from any cause). Patients alive without event will be censored at the date of the last follow-up (12). The 3-year DFS rate will be estimated using Kaplan Meier method.

Secondary endpoints 4

1. Efficacy endpoints :Disease Free Survival will be defined as time from randomization to first event. Patients alive without event will be censored at the date of the last follow. Overall Survival defined as the time from the date of randomization to the date of documented death from any cause. Patients alive at the end of the study will be censored at the date of the last contact. Time to Recurrence is defined as the time from the date of randomization to the date of first recurrence
2. Safety endpoints :Safety of treatments (NCI-CTCAE version 6.0) will be determined through the incidence of adverse events (AEs), treatment related adverse events (TRAEs), serious adverse Events (SAE), and death. For ctDNA-negative cohort: Rate of neurotoxicity in each arm in de-escalation cohort (CAPOX vs CAPE), along with comparison between two arms of severity and duration of such neurotoxicity during treatment and at 1 year after treatment.
3. Exploratory endpoints : Quality of life. Identify prognostication of stage III CRC by testing the added value of ctDNA on classical histoprognostic factors. Value of biological factors will be described by absolute or relative variation from baseline. To assess their prognostic or predictive values of DFS/OS, baseline values of these biomarkers will be tested using Cox reg model. For ctDNA-negative: Rate of ctDNA positivation. For ctDNA-positive: Rate of ctDNA negativation
4. Ancillary studies endpoints: To evaluate several ctDNA detection technics (methylation, sequencing…). To assess the incremental prognostic value contributed by various tumor molecular signatures relative to ctDNA status.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications