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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,660
- 试验地点
- 2
- 主要终点
- The time to recurrence (TTR)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Surveillance inside the trial/control arm
干预措施: Thoracic-abdomino-pelvic scan or MRI (Other)
Surveillance inside the trial/control arm
干预措施: Questionnaires (Other)
Chemotherapy by FOLFIRI
干预措施: "FOLFIRI" cures (Drug)
Chemotherapy by FOLFIRI
干预措施: BIOLOGICAL ASSESSMENT (Biological)
Chemotherapy by FOLFIRI
干预措施: Questionnaires (Other)
Chemotherapy by FOLFIRI
干预措施: Thoracic-abdomino-pelvic scan or MRI (Other)
Chemotherapy by Trifluridine tipiracil
干预措施: BIOLOGICAL ASSESSMENT (Biological)
Chemotherapy by Trifluridine tipiracil
干预措施: Questionnaires (Other)
Chemotherapy by Trifluridine tipiracil
干预措施: Thoracic-abdomino-pelvic scan or MRI (Other)
Surveillance inside the trial/control arm
干预措施: BIOLOGICAL ASSESSMENT (Biological)
Chemotherapy by Trifluridine tipiracil
干预措施: Trifluridine cures (Drug)
结局指标
主要结局
The time to recurrence (TTR)
时间窗: 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.
次要结局
未报告次要终点