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

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)

Overview

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).

Interventions

• 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
• Procedure Transanal Endoscopic Microsurgery
  Standard surgical treatment of T1, N0, M0 rectal cancer. Early after diagnosis

Primary outcome measures

• Rectal preservation in T1,N0,M0 rectal cancer [Time frame: 2 years]
• Total mesorectal excision in T1,N0,M0 rectal cancer [Time frame: 2 years]

Secondary outcome measures (6)

• Analysis of tolerance and side effects of preoperative chemoradiotherapy (CRT). [Time frame: 30 days after preoperative CRT]
• Postoperative morbidity and mortality in both groups. [Time frame: 30 days after surgery]
• The clinical and pathological response of patients undergoing CRT. [Time frame: 30 days after surgery]
• Quality of life one year after surgery. [Time frame: One year after surgery]
• Local recurrence in both groups [Time frame: At two years]
• 3-year survival results in both groups, [Time frame: Three years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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, phas PMID 36220461
• 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
• 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
• 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 PMID 29234923
• 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
• Serra-Aracil X, Nonell A, Gener-Jorge C, Pericay C, Golda T, Kreisler E, Espin-Basany E, Pallisera A, Badia-Closa J, Espina B, Borda-Arrizabalaga N, Reina A, Guadalajara-Labajo H, Otero A, Delgado S, Kraft M, Querol R, Flor B, Pellino G, Biondo S, Caro-Tarrago A; TAUTEM-T1 collaborative group. Chemoradiotherapy and transanal endoscopic surgery versus transanal endoscopic surgery alone in T1N0M0 re PMID 42026347

Identifiers

NCT: NCT06450574 · TAUTEM-T1_2024-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗