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

University Hospital Center (CHU) Dijon Bourgogne

Status and phase: Not yet enrolling; Phase 3

Conditions: Colon or Upper Rectum Adenocarcinoma

Treatments: Other: Questionnaires; Drug: Trifluridine cures; Drug: "FOLFIRI" cures; Other: Thoracic-abdomino-pelvic scan or MRI; Biological: BIOLOGICAL ASSESSMENT

Study type: Interventional

Funder types: Other

Identifiers

NCT06197425

LEPAGE PHRCK 2022

Details and patient eligibility

About

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

Enrollment: 1,660 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,660 participants in 4 patient groups

Chemotherapy by FOLFIRI

Experimental group

Treatment:

Drug: "FOLFIRI" cures

Other: Questionnaires

Other: Thoracic-abdomino-pelvic scan or MRI

Biological: BIOLOGICAL ASSESSMENT

Chemotherapy by Trifluridine tipiracil

Experimental group

Treatment:

Drug: Trifluridine cures

Other: Questionnaires

Other: Thoracic-abdomino-pelvic scan or MRI

Biological: BIOLOGICAL ASSESSMENT

Surveillance inside the trial/control arm

Active Comparator group

Treatment:

Other: Questionnaires

Other: Thoracic-abdomino-pelvic scan or MRI

Biological: BIOLOGICAL ASSESSMENT

Surveillance outside the trial

No Intervention group