The Efficacy of Primary Total Mesorectal Excision (TME) Surgery Versus Neoadjuvant Chemotherapy Combined With TME Surgery in Low-risk Locally Advanced Rectal Cancer (TaLaR-02)

TME vs TME+nCT in Low-risk LARC

Comparative analysis of the clinical efficacy between primary Total Mesorectal Excision (TME) surgery and neoadjuvant chemotherapy combined with TME surgery for low-risk locally advanced rectal cancer. Randomly enrolling eligible patients into either the control group receiving neoadjuvant chemotherapy combined with TME surgery or the experimental group receiving primary TME surgery, and subsequently comparing the clinical outcomes of the two groups

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: total mesorectal excision; Procedure: neoadjuvant chemotherapy plus total mesorectal excision

• Study Type: Interventional
• Enrollment (Estimated): 766
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Huashan Liu, MD. PhD; Phone Number: +8613560309975; Email: liuhshan@mail2.sysu.edu.cn
• Study Contact Backup: Name: Ziwei Zeng, MD,PhD; Phone Number: +8615521161750; Email: zengzw@mail2.sysu.edu.cn

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Recruiting
      • Daping Hospital, Amy Medeical Univerisity
      • Contact: Weidong Tong, MD,PhD; Phone Number: +8613500321218; Email: vdtong@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • Sun yat-sen University, the Sixth Affiliated Hospital
      • Contact: Liang Kang, MD, PhD; Phone Number: +8613602886833; Email: kangl@mail.sysu.edu.cn
      • Contact: Huashan Liu, MD, PhD; Phone Number: +8613560309975; Email: liuhshan@mail2.sysu.edu.cn
  • Hunan
    • Hengyang, Hunan, China, 421001
      • Recruiting
      • The First Affiliated Hospital of University of South China
      • Contact: Jun Ouyang, MD,PhD; Phone Number: +8613973426200; Email: 1847039906@qq.com
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Hong Zhang, MD,PhD; Phone Number: +8618940257919; Email: haojiubujian1203@sina.cn
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Yongchun Song, MD,PhD; Phone Number: +8618991232549; Email: dr.songyongchun@qq.com
  • Sichuan
    • Nanchong, Sichuan, China, 637000
      • Recruiting
      • The Affiliated Nanchong Central Hospital of North Sichuan Medical College
      • Contact: Mingyang Ren, MD,PhD; Phone Number: +8613890756658; Email: 281746489@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed patients, aged 18 to 75 years;
2. Pathologically confirmed rectal adenocarcinoma;
3. Distance of the lower margin of the rectal tumor lesion from the anal margin <15cm;
4. High-resolution MRI indicates low-risk locally advanced rectal cancer: T1-3bN1-2 or T3aN0 or T3bN0; no involvement of the anal sphincter; negative mesorectal fascia (MRF) status; negative extramural vascular invasion (EMVI); no cancer nodules;
5. Exclusion of patients with non-local recurrence or distant metastases;
6. Absence of synchronous colorectal multiple primary cancers;
7. Adequate physical condition to tolerate surgery and neoadjuvant chemotherapy, including cardiac, pulmonary, hepatic, and renal functions;
8. The study physician assessed no difficulty in sphincter preservation;
9. patients and their families will be willing to participate in this study and provide written informed consent.

Exclusion Criteria:

1. Patients with concurrent other malignancies or a history of malignant tumors in the past;
2. Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgery;
3. Patients with tumor invasion into the external sphincter or levator ani muscles, or involvement of adjacent organs necessitating combined organ resection;
4. Patients with poor anal function or fecal incontinence before surgery;
5. Patients with a history of inflammatory bowel disease or familial adenomatous polyposis;
6. Patients recently diagnosed with other malignancies;
7. Patients with ASA grade ≥ IV and/or ECOG performance status score > 2;
8. Patients with severe liver or kidney dysfunction, significant cardiopulmonary impairment, coagulation disorders, or those with extreme underlying conditions unable to tolerate surgery;
9. Patients with a history of severe mental illness;
10. Pregnant or lactating women;
11. Patients with uncontrolled infections before surgery;
12. Patients with other clinical or laboratory conditions, as determined by the investigator, that render them unsuitable for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary total mesorectal excision; Patients with low-risk locally advanced rectal cancer received total mesorectal excision alone.	Procedure: total mesorectal excision; Standard total mesorectal excision
Active Comparator: Neoadjuvant chemotherapy plus TME; Patients with low-risk locally advanced rectal cancer received neoadjuvant chemotherapy and total mesorectal excision.	Procedure: neoadjuvant chemotherapy plus total mesorectal excision; Neoadjuvant chemotherapy regimen recommended FOLFOX6, XELON, FOLFOX, mFOLFOX for 4-6 courses, and TME surgical treatment after preoperative tumor restaging 1-2 weeks after neoadjuvant chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Disease Free Survival	Defined as the proportion of patients who did not experience any of the following events from the beginning of the randomized subgroup to the end of the third year, which included disease progression, local recurrence, distant metastasis, or second primary colorectal cancer, or death from any cause.	3 years after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distance from the inferior resection margin to the tumor	The length between inferior resection margin and the tumor.	Immediately after the surgery
The status of circumferential margin	When the distance from the tumor or malignant lymph node to the circumferential margin was ≤ 1 mm, it was recorded as a positive circumferential margin.	Immediately after the surgery
The status of distal resection margin	When the distance from the tumor to the distal resection margin was ≤ 10 mm, it was recorded as a positive distal resection margin.	Immediately after the surgery
Postiveoperative stay	The days after surgery in the hospital	1 months after surgery
Time to Postoperative first feed	The duration after surgery to first feed	1 months after surgery
Time to Postoperative first gas	The duration after surgery to first gas	1 months after surgery
Postoperative pain	Postoperative pain according to pain socres	1 months after surgery
Postoperative anal function	Anal function would be based on wexner Incontinence score. A total score of less than ten is considered good, and a score of more than ten is considered poor.	3 years after the surgery
Quality of life score	Quality of life score would be based on EORTC QoL C30 scale.	3 years after the surgery
3-year overall survival		3 years after the surgery
5-year Disease Free Survival		5 years after the surgery
5-year overall survival		5 years after the surgery
Number of participants with treatment-related adverse events	It would be assessed by CTCAE v4.0	1 month after neoadjuvant chemotherapy

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Liang Kang, PhD,MD, Sun yat-sen University, Sixth Affiliated Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Rectal cancer; neoadjuvant chemotherapy; total mesorectal excision
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: GIHSYSU-TaLaR-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Reasonable requests can provide relevant data, but must be used anonymously

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No