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

NCT06450574 | Not Yet Recruiting Phase 3

• 1 other identifier: TAUTEM-T1_2024-01
• Study Type: interventional
• Target: 106
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Rectal Cancer Stage I

Keywords

Preoperative chemoradiotherapy; Transanal endoscopic microsurgery; Rectal Cancer; T1-N0-M0 Rectal cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Analysis of tolerance and side effects of preoperative chemoradiotherapy (CRT).

  30 days after preoperative CRT

• Postoperative morbidity and mortality in both groups.

  30 days after surgery

• The clinical and pathological response of patients undergoing CRT.

  30 days after surgery

• Quality of life one year after surgery.

  One year after surgery

• Local recurrence in both groups

  At two years

Study Arms (2)

Chemoradiotherapy+TEM

EXPERIMENTAL

Preoperative chemotherapy: capecitabine 825 mg/m2 every 12 hours orally, plus Radiotherapy (50.4 Gy). After 10 weeks, transanal endoscopic microsurgery (TEM) is done

Drug: Capecitabine (Xeloda); Radiation: 50.4 Gy; Procedure: Transanal Endoscopic Microsurgery (TEM)

ransanal endoscopic microsurgery (TEM)

ACTIVE COMPARATOR

Transanal endoscopic microsurgery (TEM)

Procedure: Transanal Endoscopic Microsurgery

Interventions

Capecitabine (Xeloda) DRUG

Capecitabine 825 mg/m2 every 12 hours orally on days of radiotherapy

Chemoradiotherapy+TEM

50.4 Gy RADIATION

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

Chemoradiotherapy+TEM

Transanal Endoscopic Microsurgery (TEM) PROCEDURE

10 weeks after Chemoradiotherapy

Also known as: Transanal Endoscopic Operation (TEO), Transanal Minimal Invasive Surgery (TAMIS)

Chemoradiotherapy+TEM

Transanal Endoscopic Microsurgery PROCEDURE

Standard surgical treatment of T1, N0, M0 rectal cancer. Early after diagnosis

Also known as: Transanal Endoscopic Operation (TEO), Transanal Minimal Invasive Surgery (TAMIS)

ransanal endoscopic microsurgery (TEM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Corporacion Parc Tauli: lead

Related Publications (5)

• 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.

  PMID: 36220461 BACKGROUND

• 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.

  PMID: 37061250 BACKGROUND

• 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.

  PMID: 33629231 BACKGROUND

• 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-T3s (superficial) N0, M0 undergoing neoadjuvant treatment and local excision (TEM) vs total mesorectal excision (TME). Int J Colorectal Dis. 2018 Feb;33(2):241-249. doi: 10.1007/s00384-017-2942-1. Epub 2017 Dec 12.

  PMID: 29234923 RESULT

• 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 available.

  PMID: 4155346 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Transanal Endoscopic Microsurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Transanal Endoscopic Surgery; Natural Orifice Endoscopic Surgery; Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Proctoscopy; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Digestive System Surgical Procedures; Surgical Procedures, Operative; Microsurgery; Minimally Invasive Surgical Procedures

Central Study Contacts

Xavier Serra-Aracil, MD

CONTACT

+34937231010; jserraa@tauli.cat

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor. Medical Doctor

Study Record Dates

• First Submitted: May 19, 2024
• First Posted: June 10, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: June 10, 2024

Record last verified: 2024-05