Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy (TELEPHOME)

• ClinicalTrials.gov Identifier: NCT03587480
• Recruitment Status: Recruiting
• First Posted: July 16, 2018
• Last Update Posted: November 25, 2022
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Information provided by (Responsible Party): Sixth Affiliated Hospital, Sun Yat-sen University

Study Description

Brief Summary:

Treatment for Low rectal cancer, especially in patients with regional lymph node metastasis are quite different between Japanese guideline (JSCCR) and western countries' guideline (NCCN, ESMO). While Japanese scholars advocate total mesorectal excision (TME) plus lateral lymph node dissection (LLND), European and American scholars advocate TME alone after Neoadjuvant Chemo-radiotherapy (nCRT), without the need of LLND. Accordingly, this clinical trial is designed to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. It will provide high-level clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Condition or disease	Intervention/treatment	Phase
Rectal Neoplasm Malignant	Procedure: TME+LLND; Procedure: TME+nCRT	Not Applicable

Detailed Description:

There are significant differences between Japanese guidelines (JSCCR) and Western guidelines (NCCN, ESMO) in the treatment of low rectal cancer, especially in patients with regional lymph node metastasis. Japanese scholars advocated total meso rectal resection (TME) + Lateral lymph node dissection (LLND), However, European and American scholars advocate that only TME is used after new adjuvant chemo-radiation (nCRT), without LLND. Therefore, the purpose of this clinical trial was to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. This will provide a high level of clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy of Lower Rectal Cancer With Suspected Local Lymph Node Metastasis
• Actual Study Start Date: December 17, 2018
• Estimated Primary Completion Date: May 24, 2025
• Estimated Study Completion Date: May 24, 2030

Arms and Interventions

Arm	Intervention/treatment
TME+LLND group; Total Mesorectal Excision plus Lateral Lymph Node Dissection for low rectal cancer with regional lymph node metastasis.	Procedure: TME+LLND; patients in TME+LLND group receive Lateral Lymph Node Dissection (LLND) after Total Mesorectal Excision(TME)
TME+nCRT group; Total Mesorectal Excision After Neoadjuvant Chemo-radiotherapy for low rectal cancer with regional lymph node metastasis.	Procedure: TME+nCRT; patients in TME+nCRT group receive Neoadjuvant Chemo-radiotherapy (nCRT) before Total Mesorectal Excision(TME)

Outcome Measures

Primary Outcome Measures :

1. 3-year disease-free survival [ Time Frame: From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years ]
   36 months after surgery

Secondary Outcome Measures :

1. Operative time [ Time Frame: Operation day ]
   Operation day
2. Blood loss [ Time Frame: Operation day ]
   in the perioperative period
3. Incidence of sexual dysfunction [ Time Frame: 3 years ]
   From the date of operation until the date of complication,assessed up to 3 years
4. Incidence of urinary dysfunction [ Time Frame: 3 years ]
   From the date of operation until the date of complication,assessed up to 3 years
5. Incidence of defecation dysfunction [ Time Frame: 3 years ]
   From the date of operation until the date of complication,assessed up to 3 years
6. incidence of Postoperative complications [ Time Frame: 3 months ]
   From the date of operation until the date of complication,assessed up to 3 months
7. overall survival [ Time Frame: From the date of operation until the date of death,assessed up to 5 years ]
   60 months after surgery
8. 3-year local recurrence rate [ Time Frame: From date of operation until the date of local-recurrence (up to 3 years) ]
   36 months after surgery
9. 5-year disease-free survival [ Time Frame: From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years ]
   60 months after surgery
10. the score of quality of life [ Time Frame: 3 months after operation ]
    The study investigate the quality of life using the WHOQOL Scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma(below the peritoneal reflection) Clinical stage Ⅲ
2. Tumor is capable of performing radical recession
3. No past history of chemotherapy, pelvic radiation of other cancers.
4. Written informed consent
5. Lower tumor margin is confirmed below the peritoneal reflection
6. Clinical state T(1-3)N(1-2)M0 is confirmed by the multiple disciplines team(MDT) including surgeons,diagnostic radiologist,radiation oncologist and medical oncologists base on MRI and endorectal ultrasound -

Exclusion Criteria:

1. Past history of other cancers
2. Multiple Primary Colorectal Cancers or Familial adenomatous polyposis(FAP)
3. Combine with inflammatory bowl disease(IBD)
4. Recurrence tumor or invade other organs
5. Combine with obstruction,perforation or bleeding which need emergency surgery.
6. Local tumor invade the external sphincter, levator ani muscle or adjacent organs
7. Participant join other clinical trials in 4 weeks.
8. American Society of Anesthesiologists(ASA) ≥Ⅳ and/or Eastern Cooperative Oncology Group(ECOG) ≤2
9. Pregnant or lactating patients
10. Severity infection before operation
11. Psychological disorder
12. Severe dysfunction of organs or other contraindications
13. Cardiac infarction within six months
14. Severe pulmonary emphysema and pulmonary fibrosis
15. Doctor's decision for exclusion
16. Operative findings:

Tumor invade other organs Lower tumor margin is above the peritoneal reflection

Contacts and Locations

Contacts

Contact: Yanxin Luo; 020-38250745; luoyx25@mail.sysu.edu.cn

Contact: Shaoyong Peng; 86-13435613566; pengshy9@mail2.sysu.edu.cn

Locations

China, Guangdong

The Sixth Affiliate Hospital of Sun Yat-Sen University; Recruiting

GuangZhou, Guangdong, China

Contact: Yanxin Luo, PhD,MD 86-13826190263 luoyx25@mail.sysu.edu.cn

Contact: Shaoyong Peng, MD 86-13435613566 pengshy9@mail2.sysu.edu.cn

Sponsors and Collaborators

Sixth Affiliated Hospital, Sun Yat-sen University

Investigators

• Principal Investigator: Yanxin Luo; Sixth Affiliated Hospital, Sun Yat-sen University

More Information

Publications of Results:

Shinagawa T, Tanaka T, Nozawa H, Emoto S, Murono K, Kaneko M, Sasaki K, Otani K, Nishikawa T, Hata K, Kawai K, Watanabe T. Comparison of the guidelines for colorectal cancer in Japan, the USA and Europe. Ann Gastroenterol Surg. 2017 Dec 19;2(1):6-12. doi: 10.1002/ags3.12047. eCollection 2018 Jan.

Fujita S, Akasu T, Mizusawa J, Saito N, Kinugasa Y, Kanemitsu Y, Ohue M, Fujii S, Shiozawa M, Yamaguchi T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial. Lancet Oncol. 2012 Jun;13(6):616-21. doi: 10.1016/S1470-2045(12)70158-4. Epub 2012 May 15.

Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Kinugasa Y, Komori K, Ohue M, Ota M, Akazai Y, Shiozawa M, Yamaguchi T, Bandou H, Katsumata K, Murata K, Akagi Y, Takiguchi N, Saida Y, Nakamura K, Fukuda H, Akasu T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial. Ann Surg. 2017 Aug;266(2):201-207. doi: 10.1097/SLA.0000000000002212.

Nagawa H, Muto T, Sunouchi K, Higuchi Y, Tsurita G, Watanabe T, Sawada T. Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy. Dis Colon Rectum. 2001 Sep;44(9):1274-80. doi: 10.1007/BF02234784.

Ogura A, Akiyoshi T, Nagasaki T, Konishi T, Fujimoto Y, Nagayama S, Fukunaga Y, Ueno M, Kuroyanagi H. Feasibility of Laparoscopic Total Mesorectal Excision with Extended Lateral Pelvic Lymph Node Dissection for Advanced Lower Rectal Cancer after Preoperative Chemoradiotherapy. World J Surg. 2017 Mar;41(3):868-875. doi: 10.1007/s00268-016-3762-0.

Other Publications:

Ito M, Kobayashi A, Fujita S, Mizusawa J, Kanemitsu Y, Kinugasa Y, Komori K, Ohue M, Ota M, Akazai Y, Shiozawa M, Yamaguchi T, Akasu T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Urinary dysfunction after rectal cancer surgery: Results from a randomized trial comparing mesorectal excision with and without lateral lymph node dissection for clinical stage II or III lower rectal cancer (Japan Clinical Oncology Group Study, JCOG0212). Eur J Surg Oncol. 2018 Apr;44(4):463-468. doi: 10.1016/j.ejso.2018.01.015. Epub 2018 Jan 17.

Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. doi: 10.1200/JCO.2016.66.6198. Epub 2016 Aug 1.

Qin Q, Ma T, Deng Y, Zheng J, Zhou Z, Wang H, Wang L, Wang J. Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum. 2016 Oct;59(10):934-42. doi: 10.1097/DCR.0000000000000665.

Huang M, Lin J, Yu X, Chen S, Kang L, Deng Y, Zheng J, Luo Y, Wang L, Lan P, Wang J. Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report. Int J Colorectal Dis. 2016 Jul;31(7):1349-57. doi: 10.1007/s00384-016-2605-7. Epub 2016 Jun 6.

• Responsible Party: Sixth Affiliated Hospital, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT03587480
• Other Study ID Numbers: Luo-20180624
• First Posted: July 16, 2018
• Last Update Posted: November 25, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Sixth Affiliated Hospital, Sun Yat-sen University:

Low rectal cancer; Total Mesorectal Excision (TME); neoadjuvant Chemo-radiotherapy (nCRT); lateral lymph node dissection (LLND)

Additional relevant MeSH terms:

Rectal Neoplasms; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases