Comparison Between Tailored Surgery Versus Total Mesorectal Excision in ycT2-3N0M0

NCT ID: NCT05164315

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-03
• Study Completion Date: 2024-08-26

Brief Summary

The purpose of this study is to show that tailored treatment based on local excision can expand the target of non-radical treatment in ycT2-3N0M0 patients after neoadjuvant chemoradiotherapy for low rectal cancer and that the oncologic safety is not inferior to that of total mesorectal excision.

Detailed Description

Target number of subjects and calculation basis This study aims to show that the tailored treatment based on intraoperative local excision/biopsy is not oncologically inferior to total mesorectal excision. The 5-year overall survival rate expected from the existing standard treatment was 85% (van der Valk. 2018, Rullier. 2020). The non-inferior margin of the customized treatment was 10%, type 1 error 0.10, power 80%, 1:1 ratio. When calculated with a 10% dropout rate, a total of 346 people, 173 in each group, needs to be recruited.

Study Subject Recruitment Plan

1. Selection and enrollment of subjects: Subjects in clinical trials must be enrolled by the investigator before starting surgical treatment.

2. Document consent: To the patient who is considered to be able to participate in the clinical trial as a subject, an oral explanation of this clinical trial will be presented to the participants, and the written consent to participate in the clinical trial shall be obtained.

3. Preoperative evaluation A pre-treatment examination to determine the selection of subjects and their underlying condition will be conducted. Pre-treatment examination will be performed to review whether the subject meets the selection and exclusion criteria, and subjects with significant abnormalities will be excluded.

Control group setting and randomization method Tailored treatment based on local excision and total mesorectal excision are randomly assigned 1:1 by web-based random number table (REDCap).

Statistical Analysis The statistical analyses will be conducted using intention-to-treat, and per-protocol approaches. Multiple imputation for missing covariates will be performed to determine whether there are systematic differences in terms of missing data. Analyses of the primary and secondary outcomes will be adjusted for potential co-variates.

Results of the quality of life and sexual/urinary function questionnaires will be compared using linear generalized estimating equations (GEE), adjusted for baseline values, the time effect, and the interaction effect between time and treatment.

Clinical and pathological variables will be compared using χ2 tests or Fisher's exact test for categorical variables, or with Student's t-test for continuous variables. Disease-free survival, relapse-free survival, and overall survival curves will be plotted using the Kaplan-Meier method, and differences in survival curves will be compared using the log-rank test. Multivariable analyses using the Cox regression hazard model will be conducted to identify the factors that are independently associated with disease-free survival, relapse-free survival, and overall survival. All statistical tests will be two-sided and values of p<0·05 will be considered statistically significant.

Conditions

Rectal Cancer, Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tailored surgery

Arm 1 will receive tailored surgery. If there are no cancer cells or the margin is negative in the local excision/biopsy during surgery, the operation will be terminated. And if the final pathology result is T2-4, or cancer cells and margin are positive in the frozen section during surgery, or the result of digital rectal examination and visual examination using anoretractor under general anesthesia is not suitable for local excision (visible and palpable tumor nodules), a total mesorectal excision will be performed.

Group Type: EXPERIMENTAL

Tailored surgery

Intervention Type: PROCEDURE

Procedure: Tailored surgery based on intraoperative local excision/biopsy

Total mesorectal excision (TME)

Arm 2 will receive TME. Surgery including high ligation of the inferior mesenteric artery and total mesorectal excision will be performed under the lithotomy position. After pelvic dissection, double-stapled anastomosis or transanal anastomosis will be performed, followed by diverting stoma. Abdominoperineal resection with permanent stoma is included.

Group Type: ACTIVE_COMPARATOR

Total mesorectal excision (TME)

Intervention Type: PROCEDURE

Procedure: Total mesorectal excision for all allocated patients

Interventions

Tailored surgery

Procedure: Tailored surgery based on intraoperative local excision/biopsy

Intervention Type: PROCEDURE

Total mesorectal excision (TME)

Procedure: Total mesorectal excision for all allocated patients

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed diagnosis of adenocarcinoma of the rectum (AV≤5cm)
• Clinical ycT2-3N0 based on MRI after neoadjuvant chemoradiotherapy (including long/short-course chemoradiotherapy, total neoadjuvant therapy etc…)
• No evidence of distant metastases
• No prior pelvic radiation therapy
• No prior chemotherapy or surgery for rectal cancer
• Age 18 to 80 years
• No active infections requiring systemic antibiotic treatment (oral antibiotics are acceptable at the discretion of the treating physician)
• Women with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. A woman of childbearing potential is defined of one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study.
• Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Patients who do not read or understand Korean are eligible and may be consented according to institutional and federal regulations.
• Hemoglobin ≥ 10 g/dl (after correction for simple iron deficiency anemia), White blood cells ≥ 4,000/mm3, Platelets ≥ 100,000/mm3, Creatinine ≤ 1.5 mg/dl
• No significant dysfunction in the heart or lungs: When it is judged that the risk related to surgery due to functional impairment is not high during consultation treatment

Exclusion Criteria

• Metastasis to the liver, lung, brain, bone, abdominal aortic lymph node, subclavian lymph node, inguinal lymph node, etc. at the time of evaluation before treatment
• Patients with a history of a prior malignancy
• Patients with serious heart disease and heart failure, severe lung disease or pulmonary insufficiency, active bacterial infection requiring parenteral antibiotic administration and/or other serious medical conditions
• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study.
• When it is legally impossible to participate in a clinical trial
• Patients who are pregnant or lactating
• When existing diseases and disorders are expected to affect the quality of life evaluation after surgery

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sung-Bum Kang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Seoul National University Bundang Hospital

Seongnam, , South Korea

Countries

South Korea

Other Identifiers

B-2107-697-002

Identifier Type: -

Identifier Source: org_study_id