Capecitabine for Rectal cancer

Inclusion criteria

• {"criterion_text":"- The patient has had an endoluminal local excision (by TEM, TAMIS, TSPM, EMR, ESD, endoscopic full thickness resection, endoscopic intramuscular dissection or polypectomy) of an early rectal cancer without carcinoma in the resection plane.\n- Patients with unreliable resection planes (EMR/ESD) are eligible for randomisation if no macroscopic residual tumour is found during endoscopy.\n- Patients with carcinoma in the resection plane are eligible for randomisation after re-excision that shows no carcinoma in the resection plane.\n- Only lesions for which TME surgery is indicated can be included (if a partial mesorectal excision (PME) is indicated the patient should be excluded).\n- Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: T1 with size 3-5 cm of carcinoma or pT1, maximum size of carcinoma of 3 cm, with at least poor differentiation, Haggit 4 and/or sm3, tumour budding, lymphatic and/or venous invasion.\n- Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: pT2, maximum size of carcinoma of 3 cm, well/moderate differentiated and without lymphatic or venous invasion.\n- Complete colonoscopy, without synchronous colorectal cancer.\n- cN0 stage based on pelvic MRI; lymph nodes smaller than 10 mm will be considered as benign, independent of morphologic features. Staging done within 6 weeks before randomisation.\n- Adequate distant staging (X-thorax or CT-thorax and CT-abdomen) without signs of distant metastasis (cM0).\n- Male or female, age > 18 years.\n- Life expectancy of at least 12 months.\n- Medically fit (WHO 0-2) to undergo radical surgery and/or radiation.\n- No contraindications to chemotherapy, including adequate blood counts; white blood count >= 4.0 x 10 9/l, platelet count >=100 x 109/l, clinical acceptable haemoglobin levels, bilirubin < 35 umol/l, creatinine levels indicating renal clearance of >=50 ml/min\n- The patient is willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.\n- Written (signed and dated) informed consent and be capable of co-operating with protocol."}

Exclusion criteria

• {"criterion_text":"- Incomplete or inconclusive resection margin with macroscopic residual tumour.\n- T1 tumour with carcinoma <3 cm, moderate/well differentiated, without sm3/Haggit4, tumour budding, venous or lymphatic invasion.\n- T1 tumour with carcinoma of >5 cm and T2 tumour with carcinoma of >3 cm.\n- Presence of metastatic disease or recurrent rectal tumour.\n- Previous pelvic radiation.\n- Treatment with any other investigational agent, or participation in another clinical trial that might influence study outcomes within 28 days prior to enrolment.\n- Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.\n- Pregnancy, breast-feeding or fertile women without active birth control.\n- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (<6 months prior to randomisation), myocardial infarction (<6 months prior to randomisation), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.\n- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.\n- History of severe and unexpected reactions to fluoropyrimidine therapy.\n- Hypersensitivity to capecitabine.\n- Patients with severe hepatic impairment.\n- Medical or psychiatric conditions that compromise the patient's ability to give informed consent.\n- Patients known with dihydropyrimidine dehydrogenase deficiency.\n- Any contra-indications to undergo MRI imaging."}

Primary endpoints

• {"endpoint_text":"- Three-year local recurrence rate","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Short-term morbidity: treatment related morbidity that occurs during treatment or within 30 days after the allocated treatment. The Comprehensive Classification index (see appendix) (36) and the NCI CTCAE Toxicity criteria will be used to assess to degree of morbidity in both separate treatment arms.\n- Unsalvagable pelvic disease at three years, defined as locoregional recurrence that is not able to be treated with curative intent.\n- Stoma rate at one, three and five year follow-up.\n- Long-term morbidity: long-term morbidity such as surgical re-interventions and readmissions related to the primary intervention will be evaluated at one, three and five years.\n- Functional outcome and HRQoL after therapy will be measured using the validated questionnaires EQ-5D, EORTC QLQ C29 & C30 and the LARS score for functional outcomes at admission and at 3, 6, 12, 24 and 36 months post-operatively.\n- Health Economics; possible advantage of the new rectal preserving treatment in cost per quality of life adjusted life years using the EQ5D score will be analysed. The total costs will be assessed by summing the procedure related costs, in hospital stay costs, reintervention and morbidity related costs and time to return to work will be calculated in loss of work days, which can be converted to costs.\n- Disease free and overall survival at three-year and five-year follow-up.","definition_or_measurement_approach":"- Short-term morbidity: measured during treatment or within 30 days after allocated treatment using the Comprehensive Classification index and NCI CTCAE Toxicity criteria.\n- Unsalvagable pelvic disease: defined explicitly as locoregional recurrence not treatable with curative intent (assessed at three years).\n- Stoma rate: proportion of patients with a stoma at 1, 3 and 5 years follow-up.\n- Long-term morbidity: assessed as surgical re-interventions and readmissions related to primary intervention at 1, 3 and 5 years.\n- Functional outcome and HRQoL: measured using EQ-5D, EORTC QLQ C29 & C30 and LARS score at baseline and 3, 6, 12, 24 and 36 months post-operatively.\n- Health Economics: cost per QALY using EQ-5D; total costs from procedure, in-hospital stay, reintervention/morbidity costs and productivity loss (time to return to work).\n- Disease free and overall survival: assessed at 3-year and 5-year follow-up."}

Netherlands

Earliest CTIS Part Ii Submission Date

07-01-2025

Latest Decision Or Authorization Date

14-01-2025

Processing Time Days

7

Number Of Sites

33

Number Of Participants

310

France

Earliest CTIS Part Ii Submission Date

07-01-2025

Latest Decision Or Authorization Date

29-01-2025

Processing Time Days

22

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands