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

NCT06197425 | Not Yet Recruiting Phase 3

• 1 other identifier: LEPAGE PHRCK 2022
• Study Type: interventional
• Target: 1,660
• Locations: 1 country
• Sites: 1

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

Conditions

Colon or Upper Rectum Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• The time to recurrence (TTR)

  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.

  From date of randomization until the date of first documented progression or date of death from colorectal cancer

Study Arms (4)

Chemotherapy by FOLFIRI

EXPERIMENTAL

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

Chemotherapy by Trifluridine tipiracil

EXPERIMENTAL

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

Surveillance inside the trial/control arm

ACTIVE COMPARATOR

Biological: BIOLOGICAL ASSESSMENT; Other: Questionnaires; Other: Thoracic-abdomino-pelvic scan or MRI

Surveillance outside the trial

NO INTERVENTION

Interventions

"FOLFIRI" cures DRUG

(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

Chemotherapy by FOLFIRI

Trifluridine cures DRUG

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

Chemotherapy by Trifluridine tipiracil

BIOLOGICAL ASSESSMENT BIOLOGICAL

blood sample ACE markers

Chemotherapy by FOLFIRI; Chemotherapy by Trifluridine tipiracil; Surveillance inside the trial/control arm

Questionnaires OTHER

Quality of life questionnaires (QLQ-C30 ; EQ-5D-5L ; GPAQ)

Chemotherapy by FOLFIRI; Chemotherapy by Trifluridine tipiracil; Surveillance inside the trial/control arm

Thoracic-abdomino-pelvic scan or MRI OTHER

Thoracic-abdomino-pelvic scan or MRI

Chemotherapy by FOLFIRI; Chemotherapy by Trifluridine tipiracil; Surveillance inside the trial/control arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourgogne

Dijon, 21000, France

Location

MeSH Terms

Interventions

Surveys and Questionnaires; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Spectrum Analysis; Chemistry Techniques, Analytical

Central Study Contacts

Julien TAIEB

CONTACT

01 56 09 50 42; julien.taieb@egp.aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 9, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: January 9, 2024

Record last verified: 2023-12

Locations

FR (1)