Preoperative Chemoradiotherapy and Transanal Endoscopic Microsurgery Versus Ttransanal Endoscopic Microsurgery in T1 N0, M0 Rectal Cancer (TAUTEM-T1 Study)

Rectal Cancer Stage I Clinical Trial

— TAUTEM-T1  

Official title:

Prospective, Controlled and Randomized Phase III Multicentric Study of the Treatment of T1,N0,M0 Rectal Cancer. Neoadjuvant Therapy and Transanal Endoscopic Surgery vs. Transanal Endoscopic Surgery (TAUTEM-T1 Study)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06450574
• Other study ID #: TAUTEM-T1_2024-01
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 2024
• Est. completion date: October 2027

Study information

• Verified date: May 2024
• Source: Corporacion Parc Tauli
• Contact: Xavier Serra-Aracil, MD
• Phone: +34937231010
• Email: jserraa[@]tauli.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction: The standard treatment for rectal adenocarcinoma is total mesorectal excision (TME), a technique involving resection of the rectum, with or without a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. On the other hand, transanal endoscopic surgery (TEM) allows access to tumors up to 20 cm from the anal margin, with much lower postoperative morbidity and without the need for ostomy. For T1, N0, M0 rectal adenocarcinomas without poor prognostic factors, TEM is the technique of choice. However, recent studies have described local recurrences of up to 20%. Our group, TAUTEM, has just completed a phase III clinical trial in T2-T3ab, N0, M0 rectal cancer, comparing preoperative chemoradiotherapy (CRT) and TEM versus TME, with very positive results in terms of postoperative morbidity, quality of life, and a local recurrence rate of 7.4%, not inferior to TME. These results encourage our TAUTEM group to launch a similar project at the T1, N0, M0 stage, comparing standard TEM treatment versus QRT and TEM, aiming to improve rectal preservation outcomes and enhance results regarding local recurrence, distant recurrence, and oncologic survival. Method: Prospective, controlled, randomized phase III multicenter clinical trial. Patients with rectal adenocarcinoma within 10 cm of the anal margin and up to 4 cm in size, staged as T1, N0, M0, will be included. These patients will be randomized into two groups: TEM after CRT and TEM alone. Postoperative morbidity and mortality, CRT side effects, and quality of life will be recorded. The minimum follow-up will evaluate rectal preservation and local recurrence and survival at two and three years. The sample size calculation for the study will be 106 patients. Conclusions: The aim of the study is to improve oncological outcomes in stage T1, N0, M0 rectal cancer through preoperative chemoradiotherapy associated with local surgery (TEM).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 106
• Est. completion date: October 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Indication by multidisciplinary committee of indication for local excision, according to ESMO and NCCN criteria.
• Rectal adenocarcinomas in the biopsy, located at a distance from the anal margin less than or equal to 10 cm measured by rigid rectoscopy at the time of ER.
• Preoperative staging by ER and pelvic MRI of T1,N0. In case of disparity, higher staging will be considered the definitive diagnosis. If it is greater than T1, it will be excluded.
• Tumors equal to or less than 4 cm in maximum diameter measured by MRI.
• ASA index equal to or less than III.
• Absence of distant metastases by abdominal CT and chest X-ray (if inconclusive, Thoracic CT)

Exclusion Criteria:

• Preoperative staging by EER or pelvic MRI higher than T1 or N0.
• Presence of distant metastases. Synchrony with other colorectal adenocarcinomas.
• Undifferentiated rectal adenocarcinomas or with the presence of poor prognostic factors in the preoperative biopsy (undifferentiated, venous, lymphatic or perineural infiltration, budding) .
• Patients with intolerance to preoperative chemotherapy or radiotherapy.
• Do not sign informed consent.

Related Conditions & MeSH terms

• Rectal Cancer Stage I
• Rectal Neoplasms

Intervention

Drug:
• Capecitabine (Xeloda)
Capecitabine 825 mg/m2 every 12 hours orally on days of radiotherapy

Radiation:
• 50.4 Gy
Radiotherapy was administered in daily fractions of 1.8 Gy 5 days a week according to standard schema. The total dose is 45 Gy plus a boost of 5.4 Gy to the tumor area

Procedure:
• Transanal Endoscopic Microsurgery (TEM)
10 weeks after Chemoradiotherapy
• Transanal Endoscopic Microsurgery
Standard surgical treatment of T1, N0, M0 rectal cancer. Early after diagnosis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Corporacion Parc Tauli

References & Publications (5)

Casalots A, Serra-Aracil X, Mora-Lopez L, Garcia-Nalda A, Pericay C, Ferreres JC, Navarro-Soto S. T1 Rectal Adenocarcinoma: a Different Way to Measure Tumoral Invasion Based on the Healthy Residual Submucosa with Its Prognosis and Therapeutic Implications. J Gastrointest Surg. 2021 Oct;25(10):2660-2667. doi: 10.1007/s11605-021-04948-9. Epub 2021 Feb 24. — View Citation

Naik DN, Kaneda T. Biosynthesis of branched long-chain fatty acids by species of Bacillus: relative activity of three alpha-keto acid substrates and factors affecting chain length. Can J Microbiol. 1974 Dec;20(12):1701-8. doi: 10.1139/m74-263. No abstract — View Citation

Serra-Aracil X, Pericay C, Badia-Closa J, Golda T, Biondo S, Hernandez P, Targarona E, Borda-Arrizabalaga N, Reina A, Delgado S, Vallribera F, Caro A, Gallego-Plazas J, Pascual M, Alvarez-Laso C, Guadalajara-Labajo HG, Mora-Lopez L. Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phase III trial (the TAU-TEM study). Ann Oncol. 2023 Jan;34(1):78-90. doi: 10.1016/j.annonc.2022.09.160. Epub 2022 Oct 8. — View Citation

Serra-Aracil X, Pericay C, Golda T, Mora L, Targarona E, Delgado S, Reina A, Vallribera F, Enriquez-Navascues JM, Serra-Pla S, Garcia-Pacheco JC; TAU-TEM study group. Non-inferiority multicenter prospective randomized controlled study of rectal cancer T2- — View Citation

Serra-Aracil X, Pericay C. Reply to the Letter to the Editor 'The role of chemoradiotherapy in organ preservation for rectal cancer' by L. Xie, Q. Chen, and J. Zhu. Ann Oncol. 2023 Apr;34(4):440-442. doi: 10.1016/j.annonc.2022.12.011. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rectal preservation in T1,N0,M0 rectal cancer	Number of patients where local surgery has been maintained after applying the protocol exit criteria.minimum follow-up of 2 years in both groups.	2 years
Primary	Total mesorectal excision in T1,N0,M0 rectal cancer	Number of patients with Total mesorectal Excision (TME) after applying the protocol exit criteria.minimum follow-up of 2 years in both groups.	2 years
Secondary	Analysis of tolerance and side effects of preoperative chemoradiotherapy (CRT).	NCI Common Terminology Criteria for Adverse Events v3.0 after chemoradiotherapy, is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.	30 days after preoperative CRT
Secondary	Postoperative morbidity and mortality in both groups.	Postoperative (30 days post-surgery): nosocomial, surgical, and non-surgical postoperative complications; complications according to the Dindo-Clavien classification and the CCI (Comprehensive Complication Index); hospital stay.	30 days after surgery
Secondary	The clinical and pathological response of patients undergoing CRT.	The presence of a correct histological response after chemoradiotherapy is determined by the pathology study of the tumor excised after TEM, in order to establish TRG1 in Bouzourene's classification	30 days after surgery
Secondary	Quality of life one year after surgery.	Law anterior resection syndrom (LARS), Wexner incontinence scale, EORTC QLQ-C30, EORTC QLQ-CR29, and Karnofsky quality of life questionnaires. Before treatment and One year after surgery en both groups	One year after surgery
Secondary	Local recurrence in both groups	Local recurrence defined as the presence of adenocarcinoma in the biopsy on the residual scar, anastomosis, or the defect area of the excised tumor.	At two years
Secondary	3-year survival results in both groups,	3-year survival results in both groups, reflected in overall survival, disease-free survival (DFS), distant recurrence (DR), and rectal cancer survival.	Three years