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

Tracking Information

• First Submitted Date: June 28, 2018
• First Posted Date: July 16, 2018
• Last Update Posted Date: November 25, 2022
• Actual Study Start Date: December 17, 2018
• Estimated Primary Completion Date: May 24, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2022)

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

• Original Primary Outcome Measures (submitted: July 13, 2018): 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 ]

Current Secondary Outcome Measures (submitted: November 22, 2022)

• Operative time [ Time Frame: Operation day ]
  Operation day
• Blood loss [ Time Frame: Operation day ]
  in the perioperative period
• Incidence of sexual dysfunction [ Time Frame: 3 years ]
  From the date of operation until the date of complication,assessed up to 3 years
• Incidence of urinary dysfunction [ Time Frame: 3 years ]
  From the date of operation until the date of complication,assessed up to 3 years
• Incidence of defecation dysfunction [ Time Frame: 3 years ]
  From the date of operation until the date of complication,assessed up to 3 years
• incidence of Postoperative complications [ Time Frame: 3 months ]
  From the date of operation until the date of complication,assessed up to 3 months
• overall survival [ Time Frame: From the date of operation until the date of death,assessed up to 5 years ]
  60 months after surgery
• 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
• 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
• the score of quality of life [ Time Frame: 3 months after operation ]
  The study investigate the quality of life using the WHOQOL Scale

Original Secondary Outcome Measures (submitted: July 13, 2018)

• Operative time [ Time Frame: Operation 1 day ]
• Blood loss [ Time Frame: Operation 1 day ]
• Incidence of sexual,urinary and defecation dysfunction [ Time Frame: From the date of operation until the date of complication,assessed up to 3 years ]
• Postoperative complications [ Time Frame: From the date of operation until the date of complication,assessed up to 3 months ]
  including hemorrhage, leakage, infection
• overall survival [ Time Frame: From the date of operation until the date of death,assessed up to 5 years ]
• 3-year local recurrence [ Time Frame: From date of operation until the date of local-recurrence (up to 3 years) ]
• 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 ]
• Quality of life assesment [ Time Frame: 3 months after operation ]
  The study investigate the quality of life using the WHOQOL

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy
• 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
• 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
• 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rectal Neoplasm Malignant

Intervention

• Procedure: TME+LLND
  patients in TME+LLND group receive Lateral Lymph Node Dissection (LLND) after Total Mesorectal Excision(TME)
• Procedure: TME+nCRT
  patients in TME+nCRT group receive Neoadjuvant Chemo-radiotherapy (nCRT) before Total Mesorectal Excision(TME)

Study Arms

• TME+LLND group
  Total Mesorectal Excision plus Lateral Lymph Node Dissection for low rectal cancer with regional lymph node metastasis.
  Intervention: Procedure: TME+LLND
• TME+nCRT group
  Total Mesorectal Excision After Neoadjuvant Chemo-radiotherapy for low rectal cancer with regional lymph node metastasis.
  Intervention: Procedure: TME+nCRT

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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 13, 2018): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 24, 2030
• Estimated Primary Completion Date: May 24, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03587480
• Other Study ID Numbers: Luo-20180624
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sixth Affiliated Hospital, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Sixth Affiliated Hospital, Sun Yat-sen University
• Verification Date: March 2022