Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer

Rectal Cancer Clinical Trial

— TiMiSNAR  

Official title:

Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer: a Multicenter Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03465982
• Other study ID #: 1/18
• Status: Recruiting
• Phase: N/A
• Start date: June 5, 2018
• Est. completion date: June 5, 2029

Study information

• Verified date: April 2024
• Source: Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
• Contact: Igor Monsellato, MD
• Phone: +390131206506
• Email: igor.monsellato[@]ospedale.al.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and thirty-two patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. The recruiting interval will be of 5 years and the follow-up period will end 5 years after the last patient is randomized.

Description:

PURPOSE

To demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathological complete response (pCR) and reflects on disease-free survival (DFS) and overall survival (OS) rather than standard timing. Eight weeks are the current standard interval to surgery after neoadjuvant treatment, while 12 weeks represent the "minimum" longer time interval to determine further tumor modifications and the "a priori" choice to avoid hypothetical surgical detrimental effect (postoperative complications related to radiation therapy).

Primary Endpoint

• pCR

Secondary Endpoints

• DFS

• OS

• QoL (quality of Life)

Site Eligibility

The trial is a multicenter collaboration, involving all those centers able to provide the standard of cure for locally advanced rectal cancer. All the involved centers have to respect the following criteria:

• Site able to perform robotic-assisted and standard laparoscopic rectal cancer surgery and TaTME (transanal total mesorectal excision)

• Site able to provide a preoperative work up according to the work up criteria specified in this trial

• Site able to provide standard neoadjuvant treatment, both chemo and radiation therapy, according to the criteria specified in this trial

• Predicted capability to recruit a minimum of 15 patients per year to the trial.

Randomization will take place after consent is obtained and after patients have completed their baseline patient reported questionnaires. Patient consent and randomization will take place as close to the date of start of the neoadjuvant treatment as possible and must be no more than 30 days prior to planned treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: June 5, 2029
• Est. primary completion date: June 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• cT3/4N0/+M0 confirmed on CT-scan, MRI (stratification for T3a-b-c-d) 3

• Tumor starting from the distal or medium rectum (even those crossing the peritoneal reflection at distal margin, within 15 cm from the anal margin)

• Histologically-proven adenocarcinoma of the rectum

• Eligible for a resective surgery with TME (low anterior resection, intersphincteric resection, abdominoperineal resection)

• Eligible for resection by minimally-invasive surgery (standard or robotic-assisted laparoscopic procedure, all robotic systems will be accepted)

• Eligible for chemoradiation treatment

• Able to give written informed consent

• Capable of completing required questionnaires at time of consent (provided questionnaires are available in a language spoke fluently by the participant)

Exclusion Criteria:

• Metastatic disease

• Squamous carcinoma of the anal canal

• Synchronous colorectal tumors requiring multi-segment surgical resection (n.b. a benign lesion within the resection field in addition to the main cancer would not exclude a patient)

• History of psychiatric or addictive disorder or other medical condition that, in the opinion of the investigator, would preclude the patient from meeting the trial requirements

• Pregnancy

• Unable to complete neoadjuvant treatment

• Unable to give free informed consent

• Previous radiation treatment on the pelvis

• Inflammatory bowel disease

• Hereditary colorectal disease

• Previous tumors other than non-melanoma skin cancer, papillary or follicular thyroid cancer

• Participation in another rectal cancer clinical trial relating to the topic of this trial

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Procedure:
• Surgery after 8 weeks from chemoradiation treatment
Minimally invasive surgery after 8 weeks from chemoradiation treatment
• Surgery after 12 weeks from chemoradiation treatment
Minimally invasive surgery after 12 weeks from chemoradiation treatment

Locations

Country	Name	City	State
Italy	Ente Ecclesiastico ospedale generale Regionale Miulli	Acquaviva Delle Fonti
Italy	SS. Antonio e Biagio e Cesare Arrigo Hospital	Alessandria	AL
Italy	Ospedale degli Infermi	Biella
Italy	Istituto del Radio Olindo Alberti, Spedali Civili di Brescia	Brescia
Italy	Ospedale Civile Pietro Cosma	Camposampiero	Padua
Italy	ASST Ospedale di Cremona	Cremona
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Ospedale Gian Battista Morgagni - Luigi Pierantoni	Forlì	Forlì-Cesena
Italy	Ospedale Maggiore Policlinico Fondazione Ca' Granda	Milano
Italy	Ospedale San Raffaele IRCCS	Milano
Italy	Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale	Napoli
Italy	Ospedale Sacro Cuore	Negrar	Verona
Italy	Ospedale San Francesco	Nuoro
Italy	Azienda Ospedaliera San Giovanni - Addolorata	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Erlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallbook O, Syk I, Glimelius B, Martling A. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a — View Citation

Kaytan-Saglam E, Balik E, Saglam S, Akgun Z, Ibis K, Keskin M, Dagoglu N, Kapran Y, Gulluoglu M. Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer. J Cancer Res Clin Oncol. 2017 Aug;143( — View Citation

Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, — View Citation

Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer: A Meta-analysis of Published Studies. Ann Surg. 2016 Mar;263(3):458-64. doi: 10.1097/SLA.0000000000000368. — View Citation

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathologic complete response (pCR)	Pathologic Complete response on cancer defined as absence of cancer cells on specimen	8-12 weeks
Secondary	DFS	Disease Free survival	5 years
Secondary	OS	Overall Survival	5 years