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

Primary Purpose

Rectal Cancer, Adenocarcinoma

Status
Recruiting
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Tailored surgery
Total mesorectal excision (TME)
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer, Adenocarcinoma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Seoul National University Bundang HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tailored surgery

Total mesorectal excision (TME)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
The percentage of people in a study or treatment group who are alive five years after their diagnosis or the date of randomization

Secondary Outcome Measures

Immediate postoperative index
Postoperative recovery index, surgery-related complications, and mortality comparison (Clavien-Dindo classification III-V), histopathologic examination of the proximal/distal/peripheral margins
Oncologic outcomes
Rate of Disease-free Survival/Relapse-free Survival/Stoma-free Survival/Regrowth-free Survival through physical examination including digital rectal examination, carcinoembryonic antigen test (CEA), liver function test (AST/ALT), chest and abdominal CT and colonoscopy
Quality of Life evaluation
The Korean version of EORTC QLQ 30 which is an evaluation instrument for the quality of life of cancer patients, and the Korean version of EORTC QLQ-CR29 which is an evaluation instrument for the quality of life of colon cancer patients.
Sexual/urination function evaluation
IPSS (International Prostate Symptom Score) for urinary function test, IIEF-5 (5-item Version of the International Index of Erectile Function) for male sexual function test, FSFI (Female Sexual Function Index) for female sexual function test.
defecation function
MSKCC questionnaire, fecal incontinence severity index (FISI), low anterior resection syndrome (LARS) score questionnaire and fecal incontinence quality of life index (FIQL), manometry

Full Information

First Posted
November 29, 2021
Last Updated
January 5, 2022
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05164315
Brief Title
Comparison Between Tailored Surgery Versus Total Mesorectal Excision in ycT2-3N0M0
Official Title
Comparison of Oncologic Outcomes Between Tailored Surgery According to Intraoperative Local Excision Biopsy Versus Total Mesorectal Excision in ycT2-3N0M0 on Magnetic Resonance Imaging After Neoadjuvant Chemoradiotherapy for Low Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2022 (Actual)
Primary Completion Date
December 2031 (Anticipated)
Study Completion Date
December 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer, Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
346 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tailored surgery
Arm Type
Experimental
Arm Description
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.
Arm Title
Total mesorectal excision (TME)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Tailored surgery
Intervention Description
Procedure: Tailored surgery based on intraoperative local excision/biopsy
Intervention Type
Procedure
Intervention Name(s)
Total mesorectal excision (TME)
Intervention Description
Procedure: Total mesorectal excision for all allocated patients
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
The percentage of people in a study or treatment group who are alive five years after their diagnosis or the date of randomization
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Immediate postoperative index
Description
Postoperative recovery index, surgery-related complications, and mortality comparison (Clavien-Dindo classification III-V), histopathologic examination of the proximal/distal/peripheral margins
Time Frame
postoperative 30 days
Title
Oncologic outcomes
Description
Rate of Disease-free Survival/Relapse-free Survival/Stoma-free Survival/Regrowth-free Survival through physical examination including digital rectal examination, carcinoembryonic antigen test (CEA), liver function test (AST/ALT), chest and abdominal CT and colonoscopy
Time Frame
5 years
Title
Quality of Life evaluation
Description
The Korean version of EORTC QLQ 30 which is an evaluation instrument for the quality of life of cancer patients, and the Korean version of EORTC QLQ-CR29 which is an evaluation instrument for the quality of life of colon cancer patients.
Time Frame
Conduct a survey before surgery and every year after surgery until the 3rd year
Title
Sexual/urination function evaluation
Description
IPSS (International Prostate Symptom Score) for urinary function test, IIEF-5 (5-item Version of the International Index of Erectile Function) for male sexual function test, FSFI (Female Sexual Function Index) for female sexual function test.
Time Frame
Conduct a survey before surgery and every year after surgery until the 3rd year
Title
defecation function
Description
MSKCC questionnaire, fecal incontinence severity index (FISI), low anterior resection syndrome (LARS) score questionnaire and fecal incontinence quality of life index (FIQL), manometry
Time Frame
Conduct before surgery and at 1, 2, and 3 years after surgery, (at 1, 2, and 3 years after stoma restoration).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sung-Bum Kang
Phone
+82-31-787-7093
Email
kangsb@snubh.org
Facility Information:
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
ZIP/Postal Code
463-707
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung-Bum Kang, M.D., Ph.D
Phone
+82-31-787-7093
Email
kangsb@snubh.org
First Name & Middle Initial & Last Name & Degree
Duck-Woo Kim, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Heung-Kwon Oh, M.D., Ph.D.

12. IPD Sharing Statement

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

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