RecruitingPhase 3NCT06197425

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

Phase III Multicentric, Open-label, Randomized Study to Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal Cancer (PRODIGE 88)


Sponsor

Centre Hospitalier Universitaire Dijon

Enrollment

1,660 participants

Start Date

May 7, 2026

Study Type

INTERVENTIONAL

Conditions

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


Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria10

  • 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 Criteria13

  • 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.

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Interventions

DRUG"FOLFIRI" 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


Locations(1)

Chu Dijon Bourgogne

Dijon, France

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NCT06197425