Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal Cancer

Trial Title: Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal Cancer

NCT ID: NCT06197425

Condition: Colon or Upper Rectum Adenocarcinoma

Conditions: Official terms:
Colorectal Neoplasms
Adenocarcinoma
Trifluridine

Study type: Interventional

Study phase: Phase 3

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: "FOLFIRI" cures
Description: (Irinotecan 180 mg/m2, leucovorine 400mg/m2, 5FU bolus 400 mg/m2, 5FU continuous infusion 2400 mg/m2) every 14 days for 6 months or until disease progression on imaging
Arm group label: Chemotherapy by FOLFIRI

Intervention type: Drug
Intervention name: Trifluridine cures
Description: Trifluridine tipiracil 35 mg/m2 bid during 5 days/w on week 1 and 2 every 4 weeks, for 6 months or until disease progression on imaging
Arm group label: Chemotherapy by Trifluridine tipiracil

Intervention type: Biological
Intervention name: BIOLOGICAL ASSESSMENT
Description: blood sample ACE markers
Arm group label: Chemotherapy by FOLFIRI
Arm group label: Chemotherapy by Trifluridine tipiracil
Arm group label: Surveillance inside the trial/control arm

Intervention type: Other
Intervention name: Questionnaires
Description: Quality of life questionnaires (QLQ-C30 ; EQ-5D-5L ; GPAQ)
Arm group label: Chemotherapy by FOLFIRI
Arm group label: Chemotherapy by Trifluridine tipiracil
Arm group label: Surveillance inside the trial/control arm

Intervention type: Other
Intervention name: Thoracic-abdomino-pelvic scan or MRI
Description: Thoracic-abdomino-pelvic scan or MRI
Arm group label: Chemotherapy by FOLFIRI
Arm group label: Chemotherapy by Trifluridine tipiracil
Arm group label: Surveillance inside the trial/control arm

Summary: Phase III multicentric, open-label, randomized study The main objective is to assess the efficacy on time to disease recurrence (TTR) of treating minimal residual disease diagnosed by the presence of ctDNA after full treatment (surgery + chemotherapy) in stage III or high-risk stage II colon or upper rectum adenocarcinoma

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Fully resected stage III or high-risk stage II colon or upper rectum adenocarcinoma previously treated by standard adjuvant chemotherapy or peri-operative chemotherapy (FOLFOX or CAPOX) for either 3 or 6 months based on local multidisciplinary meeting, and on TNCD recommendations - Positive ctDNA screening (methylation) and confirmation (NGS) on samples collected at the 3- or 6 months follow-up visit post-adjuvant chemotherapy - Patients ≥ 18 years and ≤ 80 years (provided the score of the G8 geriatric questionnaire is >14 for patients 70 years or older) - Subjects with WHO performance status < 2 - No documented disease using TAP CT-scanner and liver MRI in the case of contra-indication to dye contrast (or TEP-scanner may be also used in addition depending on physicians' choice and local availabilities). - Adequate haematological function: with neutrophils ≥ 1,500 /mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL (5,6 mmol/l) Total bilirubin ≤ 1.5 x ULN (upper limit of normal) ASAT and ALAT ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN Creatinine clearance ≥50 ml/min according MDRD (Modification of Diet in Renal Disease) - Available tumor sample for NGS analysis - Signed written informed consent obtained prior to any study specific procedures - Patient affiliated to a social security scheme Exclusion Criteria: - Patients already treated with trifluridine tipiracil or irinotecan in the past 5 years - Uncontrolled intercurrent illness - Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease-free interval of at least 3 years - Pregnant or breastfeeding women, women of childbearing age not having had a negative pregnancy test - Any known specific contraindication or allergy to the treatments used in the study† - Total or partial dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia > 16ng/ml) - Known Gilbert's disease (UGT1A1*28 genotype) - In case of concomitant use with St John's Wort related to irinotecan - In case of bowel obstruction according related to irinotecan - In case of recent concomitant treatment with brivudine, related to fluorouracil. - Participation to another interventional study for postoperative therapy - Persons deprived of liberty or under guardianship or incapable of giving consent - Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Chu Dijon Bourgogne

Address:
City: Dijon
Zip: 21000
Country: France

Contact:
Last name: Côme LEPAGE

Phone: 03 80 29 37 50
Email: come.lepage@u-bourgogne.fr

Start date: January 2024

Completion date: January 2030

Lead sponsor:
Agency: Centre Hospitalier Universitaire Dijon
Agency class: Other

Source: Centre Hospitalier Universitaire Dijon

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06197425