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Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer (TiMiSNAR)

Primary Purpose

Rectal Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Surgery after 8 weeks from chemoradiation treatment
Surgery after 12 weeks from chemoradiation treatment
Sponsored by
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring rectal cancer, robotic rectal cancer resection, minimally invasive surgery, Colorectal Cancer, chemoradiation treatment rectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • SS. Antonio e Biagio e Cesare Arrigo HospitalRecruiting
  • Ospedale Gian Battista Morgagni - Luigi PierantoniRecruiting
  • Ospedale Civile Pietro CosmaRecruiting
  • Ospedale Sacro CuoreRecruiting
  • Ente Ecclesiastico ospedale generale Regionale MiulliRecruiting
  • Ospedale degli InfermiRecruiting
  • Azienda Ospedaliera Universitaria CareggiRecruiting
  • Ospedale Maggiore Policlinico Fondazione Ca' GrandaRecruiting
  • Ospedale San Raffaele IRCCSRecruiting
  • Istituto Nazionale Tumori - IRCCS Fondazione G. PascaleRecruiting
  • Ospedale San FrancescoRecruiting
  • Ospedale Sant' AntonioRecruiting
  • Azienda Ospedaliera San Giovanni - AddolorataRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Standard Interval Time Arm

Delayed Interval Time Arm

Arm Description

Minimally invasive surgery after 8 weeks from chemoradiation treatment

Minimally invasive surgery after 12 weeks from chemoradiation treatment

Outcomes

Primary Outcome Measures

pathologic complete response (pCR)
Pathologic Complete response on cancer defined as absence of cancer cells on specimen

Secondary Outcome Measures

DFS
Disease Free survival
OS
Overall Survival

Full Information

First Posted
February 23, 2018
Last Updated
October 15, 2021
Sponsor
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
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1. Study Identification

Unique Protocol Identification Number
NCT03465982
Brief Title
Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer
Acronym
TiMiSNAR
Official Title
Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer: a Multicenter Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 5, 2018 (Actual)
Primary Completion Date
June 5, 2024 (Anticipated)
Study Completion Date
June 5, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
rectal cancer, robotic rectal cancer resection, minimally invasive surgery, Colorectal Cancer, chemoradiation treatment rectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
340 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Interval Time Arm
Arm Type
Active Comparator
Arm Description
Minimally invasive surgery after 8 weeks from chemoradiation treatment
Arm Title
Delayed Interval Time Arm
Arm Type
Active Comparator
Arm Description
Minimally invasive surgery after 12 weeks from chemoradiation treatment
Intervention Type
Procedure
Intervention Name(s)
Surgery after 8 weeks from chemoradiation treatment
Intervention Description
Minimally invasive surgery after 8 weeks from chemoradiation treatment
Intervention Type
Procedure
Intervention Name(s)
Surgery after 12 weeks from chemoradiation treatment
Intervention Description
Minimally invasive surgery after 12 weeks from chemoradiation treatment
Primary Outcome Measure Information:
Title
pathologic complete response (pCR)
Description
Pathologic Complete response on cancer defined as absence of cancer cells on specimen
Time Frame
8-12 weeks
Secondary Outcome Measure Information:
Title
DFS
Description
Disease Free survival
Time Frame
5 years
Title
OS
Description
Overall Survival
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Igor Monsellato, MD
Phone
+390131206506
Email
igor.monsellato@ospedale.al.it
Facility Information:
Facility Name
SS. Antonio e Biagio e Cesare Arrigo Hospital
City
Alessandria
State/Province
AL
ZIP/Postal Code
15121
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Igor Monsellato, Md, PhD
First Name & Middle Initial & Last Name & Degree
Igor Monsellato, MD, PhD
First Name & Middle Initial & Last Name & Degree
Fabio Priora, MD
Facility Name
Ospedale Gian Battista Morgagni - Luigi Pierantoni
City
Forlì
State/Province
Forlì-Cesena
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Davide Cavaliere, MD
First Name & Middle Initial & Last Name & Degree
Davide Cavaliere, MD
Facility Name
Ospedale Civile Pietro Cosma
City
Camposampiero
State/Province
Padua
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enzo Mammano, MD
First Name & Middle Initial & Last Name & Degree
Emilio Morpurgo, MD
First Name & Middle Initial & Last Name & Degree
Tania Contardo, MD
Facility Name
Ospedale Sacro Cuore
City
Negrar
State/Province
Verona
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giacomo Ruffo
First Name & Middle Initial & Last Name & Degree
Giacomo Ruffo, MD
First Name & Middle Initial & Last Name & Degree
Filippo Alongi, Prof
Facility Name
Ente Ecclesiastico ospedale generale Regionale Miulli
City
Acquaviva Delle Fonti
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alessia Surgo
First Name & Middle Initial & Last Name & Degree
Alessia Surgo
First Name & Middle Initial & Last Name & Degree
Alba Fiorentino
Facility Name
Ospedale degli Infermi
City
Biella
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Perinotti, MD
First Name & Middle Initial & Last Name & Degree
Roberto Perinotti, MD
First Name & Middle Initial & Last Name & Degree
Roberto Polastri, MD
Facility Name
Azienda Ospedaliera Universitaria Careggi
City
Firenze
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Federico Perna, MD
First Name & Middle Initial & Last Name & Degree
Federico Perna, MD
First Name & Middle Initial & Last Name & Degree
Benedetta Menegatti, MD
First Name & Middle Initial & Last Name & Degree
Andrea Coratti, Prof
Facility Name
Ospedale Maggiore Policlinico Fondazione Ca' Granda
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luigi Boni, FACS
First Name & Middle Initial & Last Name & Degree
Luigi Boni, FACS
First Name & Middle Initial & Last Name & Degree
Elisa Cassinotti, MD
Facility Name
Ospedale San Raffaele IRCCS
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ugo Elmore
First Name & Middle Initial & Last Name & Degree
Ugo Elmore
Facility Name
Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Delrio, Prof
First Name & Middle Initial & Last Name & Degree
Paolo Delrio, Prof
First Name & Middle Initial & Last Name & Degree
Daniela Rega, MD
Facility Name
Ospedale San Francesco
City
Nuoro
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Pulighe, MD
First Name & Middle Initial & Last Name & Degree
Carlo De Nisco, MD
First Name & Middle Initial & Last Name & Degree
Fabio Pulighe, MD
Facility Name
Ospedale Sant' Antonio
City
Padova
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enzo Mammano
First Name & Middle Initial & Last Name & Degree
Emilio Morpurgo
First Name & Middle Initial & Last Name & Degree
Enzo Mammano
Facility Name
Azienda Ospedaliera San Giovanni - Addolorata
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Graziano Pernazza, MD
First Name & Middle Initial & Last Name & Degree
Graziano Pernazza, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
15496622
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 cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
Results Reference
result
PubMed Identifier
24263329
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.
Results Reference
result
PubMed Identifier
28190762
Citation
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.
Results Reference
result
PubMed Identifier
28374169
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(8):1597-1603. doi: 10.1007/s00432-017-2406-6. Epub 2017 Apr 3.
Results Reference
result
PubMed Identifier
27432930
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, 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.
Results Reference
result
PubMed Identifier
31842784
Citation
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.
Results Reference
derived

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Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer

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