Colon or Upper Rectum Adenocarcinoma
Conditions
Brief 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
Interventions
DRUGFOLFIRI cures
(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
DRUGTrifluridine cures
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
BIOLOGICALBIOLOGICAL ASSESSMENT
blood sample ACE markers
OTHERQuestionnaires
Quality of life questionnaires (QLQ-C30 ; EQ-5D-5L ; GPAQ)
OTHERThoracic-abdomino-pelvic scan or MRI
Thoracic-abdomino-pelvic scan or MRI
Sponsors
Centre Hospitalier Universitaire Dijon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The time to recurrence (TTR) | From date of randomization until the date of first documented progression or date of death from colorectal cancer | The time to recurrence (TTR), in patients treated by FOLFIRI vs surveillance inside the study and in patients treated by Trifluridine Tipiracil vs surveillance inside the study. This TTR is defined as time from randomization to disease recurrence including locoregional or metastatic relapse, death with evidence of recurrence and death from CRC cause. |
Countries
France
Contacts
Primary ContactJulien TAIEB
Outcome results
None listed