- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03465982
Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer (TiMiSNAR)
Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer: a Multicenter Randomised Controlled Trial
Study Overview
Status
Conditions
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Igor Monsellato, MD
- Phone Number: +390131206506
- Email: igor.monsellato@ospedale.al.it
Study Locations
-
-
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Acquaviva Delle Fonti, Italy
- Suspended
- Ente Ecclesiastico Ospedale Generale Regionale Miulli
-
Biella, Italy
- Recruiting
- Ospedale degli Infermi
-
Contact:
- Roberto Perinotti, MD
-
Principal Investigator:
- Roberto Perinotti, MD
-
Sub-Investigator:
- Roberto Polastri, MD
-
Brescia, Italy
- Recruiting
- Istituto del Radio Olindo Alberti, Spedali Civili di Brescia
-
Contact:
- Marco LF Bonù, MD
- Email: marco.bonu@unibs.it
-
Sub-Investigator:
- Vittorio Morelli, MD
-
Cremona, Italy
- Recruiting
- ASST Ospedale di Cremona
-
Contact:
- Gianluca Baiocchi, Prof
- Email: gianluca.baiocchi@unibs.it
-
Firenze, Italy
- Recruiting
- Azienda Ospedaliera Universitaria Careggi
-
Contact:
- Federico Perna, MD
-
Principal Investigator:
- Federico Perna, MD
-
Sub-Investigator:
- Benedetta Menegatti, MD
-
Sub-Investigator:
- Andrea Coratti, Prof
-
Milano, Italy
- Recruiting
- Ospedale Maggiore Policlinico Fondazione Ca' Granda
-
Contact:
- Luigi Boni, FACS
-
Principal Investigator:
- Luigi Boni, FACS
-
Sub-Investigator:
- Elisa Cassinotti, MD
-
Milano, Italy
- Recruiting
- Ospedale San Raffaele IRCCS
-
Contact:
- Ugo Elmore
-
Principal Investigator:
- Ugo Elmore
-
Napoli, Italy
- Recruiting
- Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale
-
Contact:
- Paolo Delrio, Prof
-
Principal Investigator:
- Paolo Delrio, Prof
-
Sub-Investigator:
- Daniela Rega, MD
-
Nuoro, Italy
- Terminated
- Ospedale San Francesco
-
Roma, Italy
- Suspended
- Azienda Ospedaliera San Giovanni - Addolorata
-
-
AL
-
Alessandria, AL, Italy, 15121
- Recruiting
- SS. Antonio e Biagio e Cesare Arrigo Hospital
-
Contact:
- Igor Monsellato, Md, PhD
-
Principal Investigator:
- Igor Monsellato, MD, PhD
-
Sub-Investigator:
- Fabio Priora, MD
-
-
Forlì-Cesena
-
Forlì, Forlì-Cesena, Italy
- Recruiting
- Ospedale Gian Battista Morgagni - Luigi Pierantoni
-
Contact:
- Davide Cavaliere, MD
-
Principal Investigator:
- Davide Cavaliere, MD
-
-
Padua
-
Camposampiero, Padua, Italy
- Recruiting
- Ospedale Civile Pietro Cosma
-
Contact:
- Enzo Mammano, MD
-
Principal Investigator:
- Emilio Morpurgo, MD
-
Sub-Investigator:
- Tania Contardo, MD
-
-
Verona
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Negrar, Verona, Italy
- Recruiting
- Ospedale Sacro Cuore
-
Principal Investigator:
- Giacomo Ruffo, MD
-
Contact:
- Giacomo Ruffo
-
Sub-Investigator:
- Filippo Alongi, Prof
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Standard Interval Time Arm
Minimally invasive surgery after 8 weeks from chemoradiation treatment
|
Minimally invasive surgery after 8 weeks from chemoradiation treatment
|
Active Comparator: Delayed Interval Time Arm
Minimally invasive surgery after 12 weeks from chemoradiation treatment
|
Minimally invasive surgery after 12 weeks from chemoradiation treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
pathologic complete response (pCR)
Time Frame: 8-12 weeks
|
Pathologic Complete response on cancer defined as absence of cancer cells on specimen
|
8-12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DFS
Time Frame: 5 years
|
Disease Free survival
|
5 years
|
OS
Time Frame: 5 years
|
Overall Survival
|
5 years
|
Collaborators and Investigators
Publications and helpful links
General Publications
- 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 cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
- 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.
- 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 multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017 Mar;18(3):336-346. doi: 10.1016/S1470-2045(17)30086-4. Epub 2017 Feb 10.
- 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(8):1597-1603. doi: 10.1007/s00432-017-2406-6. Epub 2017 Apr 3.
- 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, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E. Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016 Nov 1;34(31):3773-3780. doi: 10.1200/JCO.2016.67.6049.
- Monsellato I, Alongi F, Bertocchi E, Gori S, Ruffo G, Cassinotti E, Baldari L, Boni L, Pernazza G, Pulighe F, De Nisco C, Perinotti R, Morpurgo E, Contardo T, Mammano E, Elmore U, Delpini R, Rosati R, Perna F, Coratti A, Menegatti B, Gentilli S, Baroffio P, Buccianti P, Balestri R, Ceccarelli C, Torri V, Cavaliere D, Solaini L, Ercolani G, Traverso E, Fusco V, Rossi M, Priora F, Numico G, Franzone P, Orecchia S. Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR). BMC Cancer. 2019 Dec 16;19(1):1215. doi: 10.1186/s12885-019-6271-3. Erratum In: BMC Cancer. 2020 Feb 17;20(1):128.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1/18
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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