FLUOROURACIL for Rectal adenocarcinoma | Locally advanced rectal cancer

Inclusion criteria

• {"criterion_text":"- Histologically confirmed diagnosis of adenocarcinoma of the rectum\n- Patients must be affiliated to a Social Security System (or equivalent).\n- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent\n- Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures\n- Age ≥75 years\n- WHO performance status 0-1\n- cT3a-b with maximum diameter > 5 cm, T3c-d or cT4 tumor on pretreatment pelvic MRI\n- General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFOX,\n- Distal part of the tumor ≤10 cm from the anal margin, the measurement done by pelvic MRI\n- Oncogeriatrician approval\n- Adequate biological function defined by: a. Neutrophils ≥ 1500/mm3 b. Platelets ≥ 100 000/mm3 c. Hemoglobin ≥ 10g/dL d. Total bilirubin ≤ 1,5 x ULN e. Alkaline phosphatases ≤ 1,5 x ULN f. Creatinine clearance >50mL/mn (MDRD) g.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels 2.5× ULN\n- Men must agree to use adequate contraception methods during treatment and at least until 12 months after the end of the treatment with oxaliplatin"}

Exclusion criteria

• {"criterion_text":"- Metastatic disease\n- Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders).\n- Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization\n- Any psychiatric disorder precluding understanding of information of trial related topics and giving informed consent\n- No prior chemotherapy or surgery for rectal cancer\n- Any serious underlying medical condition (as judged by the investigator) that could impair the ability of the patient to participate in the trial\n- Persons deprived of their liberty or under protective custody or guardianship.\n- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.\n- Other cancer within 3 years prior to rectal cancer diagnosis (except for in situ cancer and basal cell carcinoma of the skin)\n- Non resectable cancer, including extension to prostate or extension to perineal muscles\n- History of pelvic irradiation\n- Contraindication to FOLFOX 4s chemotherapy: Regarding the treatment with 5-fluorouracil: ➢ Recent (within the last 4 weeks) or concomitant treatment with brivudine ➢ Presence of a potentially serious infection Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of the study intervention ➢ Poor nutritional status/Clinically significant active heart disease or myocardial infarction within the past 6 months, given the cardiotoxicity of fluorouracil. Regarding the treatment with oxaliplatin: Due to the cardiotoxicity of oxaliplatin (risk of QT prolongation as described in section 4.4 of the oxaliplatin SmPC): ➢ hypokalemia less than normal ➢ hypomagnesemia ➢ hypocalcemia ➢ QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG; Peripheral sensory neuropathy with functional impairment prior to the first treatment, according to the oxaliplatin SmPC. Known history of hypersensitivity to fluorouracil, oxaliplatin, folinic acid, or any of their excipients, as stated in the respective SmPCs.\n- Contraindication to MRI\n- Microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR)\n- Complete or partial Dihydropyrimidine Deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)\n- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment\n- Contradiction radiotherapy and/or TME surgery"}

Primary endpoints

• {"endpoint_text":"- The 24-months TME-free survival will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval. Organ preservation rate at 24 months, defined as proportion of patients without TME, or nonsalvageable pelvic disease, and without permanent diversion stoma. Patients alive at the time of analysis or lost from follow-up will be censored at the date of the latest news.","definition_or_measurement_approach":"Estimated with the Kaplan-Meier method and presented with 95% CI. Organ preservation rate at 24 months defined as proportion of patients without TME, or nonsalvageable pelvic disease, and without permanent diversion stoma; patients alive or lost to follow-up are censored at date of latest news."}

Secondary endpoints

• {"endpoint_text":"- Rate of cCR will be defined as percentage of CR confirmed by central review after 21 weeks divided by the number of patients. CR is defined as flat, white scar, with telangiectasia, no ulcer or nodularity on endoscopic evaluation, no induration on digital rectal examination, normal appearing bowel wall without any fibrosis in the tumor bed, dark T2 signal, no mesorectal lymph node on pelvic MRI-T2W, no visible signal on B800-B1000 MRI-DW, no metastatic dissemination on chest, abdominal CT scan","definition_or_measurement_approach":"CR confirmed by central review after 21 weeks; defined by endoscopic, clinical, MRI and CT criteria as specified above; rate = % of CRs confirmed divided by number of patients."}
• {"endpoint_text":"- The 24-month overall survival defined as the period between the date of randomization and the date of death related to the cancer. Patients who did not die at the time of analysis or are lost-of-follow-up will be censored at the date of the latest news. The 24-months OS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.","definition_or_measurement_approach":"Period between randomization and date of death related to cancer; censored if alive or lost to follow-up; estimated by Kaplan-Meier with 95% CI."}
• {"endpoint_text":"- Locoregional failure at 24 months, defined as either an unresectable rectal primary tumor following protocol neoadjuvant treatment, an R2 resection for the rectal primary tumor, or recurrence in the primary tumor bed after an R0-R1 resection. Tumor regrowth in the rectal wall or in regional lymph nodes after a cCR or near-complete response, a period of Watch & Wait or after local scar excision (for ypT0 and T1 tumor) will not be considered a locoregional failure if followed by an R0-R1 resection","definition_or_measurement_approach":"Defined events as stated (unresectable primary, R2 resection, recurrence in primary tumor bed after R0-R1); certain regrowths not counted if followed by R0-R1 resection."}
• {"endpoint_text":"- The 24-months disease-free survival defined as the period between the date of randomization and the date of locoregional failure (as described above), distant metastasis, a new invasive colorectal primary cancer, or death from any cause. The 24-months DFS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.","definition_or_measurement_approach":"Time from randomization to locoregional failure, distant metastasis, new invasive colorectal primary cancer, or death from any cause; estimated by Kaplan-Meier with 95% CI."}
• {"endpoint_text":"- 24-month Regrowth Rate will be defined as the proportion of patients presenting tumor regrowth during their surveillance in the “watch and wait” strategy or after local scar excision after they achieved cCR.","definition_or_measurement_approach":"Proportion of patients with tumor regrowth during surveillance or after local scar excision among those who achieved cCR."}
• {"endpoint_text":"- The 24-month metastasis-free survival will be defined as the period between the date of randomization and the date of detection of distant metastasis. The 24-months MFS will be estimated with the Kaplan-Meier method and presented with its 95% confidence interval.","definition_or_measurement_approach":"Time from randomization to detection of distant metastasis; estimated by Kaplan-Meier with 95% CI."}
• {"endpoint_text":"- Rate of R0 resection will be defined as the percentage of R0 resection among patients with TME surgery (for patient with surgery only)","definition_or_measurement_approach":"Percentage of R0 resections among patients undergoing TME surgery."}
• {"endpoint_text":"- Rate of postoperative complications of initial surgery will be assessed at 3 months using Clavien-Dindo classification (for patient with surgery only)","definition_or_measurement_approach":"Assessed at 3 months using Clavien-Dindo classification."}
• {"endpoint_text":"- Rate of postoperative complications of salvage surgery after initial NOM will be assessed at 3 months using Clavien-Dindo classification (for patient with surgery only)","definition_or_measurement_approach":"Assessed at 3 months using Clavien-Dindo classification."}
• {"endpoint_text":"- The safety profile in each arm will be described using the common toxicity criteria from the CTCAE v5.0.","definition_or_measurement_approach":"Safety described using CTCAE v5.0."}
• {"endpoint_text":"- The Bowel function will be assessed using the LARS score at inclusion, 3 months postradiotherapy, 12 months and 24 months post inclusion.","definition_or_measurement_approach":"Assessed using LARS score at specified timepoints."}
• {"endpoint_text":"- Quality of life will be assessed by QLQ-C30 and ELD-14 score at inclusion, 3 months postradiotherapy, 12 months and 24 months post inclusion.","definition_or_measurement_approach":"Assessed using QLQ-C30 and ELD-14 questionnaires at specified timepoints."}
• {"endpoint_text":"- Geriatric assessment will be evaluated using G8, MMS, ADL, IADL, TUG, Charlson, ACE 27, SARC F, Hand grip, 5-time chair, G Code at inclusion, then G Code at 3 months post radiotherapy, 12 and 24 months post inclusion","definition_or_measurement_approach":"Geriatric instruments listed will be used at inclusion and specified follow-up timepoints (G Code repeated at follow-ups)."}

France

Earliest CTIS Part Ii Submission Date

18-12-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

46

Number Of Sites

20

Number Of Participants

160

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France