Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer

NCT ID: NCT03465982

Last Updated: 2024-04-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-05

Study Completion Date

2029-06-05

Brief Summary

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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

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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.

Conditions

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Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Interval Time Arm

Minimally invasive surgery after 8 weeks from chemoradiation treatment

Group Type ACTIVE_COMPARATOR

Surgery after 8 weeks from chemoradiation treatment

Intervention Type PROCEDURE

Minimally invasive surgery after 8 weeks from chemoradiation treatment

Delayed Interval Time Arm

Minimally invasive surgery after 12 weeks from chemoradiation treatment

Group Type ACTIVE_COMPARATOR

Surgery after 12 weeks from chemoradiation treatment

Intervention Type PROCEDURE

Minimally invasive surgery after 12 weeks from chemoradiation treatment

Interventions

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Surgery after 8 weeks from chemoradiation treatment

Minimally invasive surgery after 8 weeks from chemoradiation treatment

Intervention Type PROCEDURE

Surgery after 12 weeks from chemoradiation treatment

Minimally invasive surgery after 12 weeks from chemoradiation treatment

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

OTHER

Sponsor Role lead

Responsible Party

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Igor Monsellato

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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SS. Antonio e Biagio e Cesare Arrigo Hospital

Alessandria, AL, Italy

Site Status RECRUITING

Ospedale Gian Battista Morgagni - Luigi Pierantoni

Forlì, Forlì-Cesena, Italy

Site Status RECRUITING

Ospedale Civile Pietro Cosma

Camposampiero, Padua, Italy

Site Status RECRUITING

Ospedale Sacro Cuore

Negrar, Verona, Italy

Site Status RECRUITING

Ente Ecclesiastico ospedale generale Regionale Miulli

Acquaviva delle Fonti, , Italy

Site Status SUSPENDED

Ospedale degli Infermi

Biella, , Italy

Site Status RECRUITING

Istituto del Radio Olindo Alberti, Spedali Civili di Brescia

Brescia, , Italy

Site Status RECRUITING

ASST Ospedale di Cremona

Cremona, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Site Status RECRUITING

Ospedale Maggiore Policlinico Fondazione Ca' Granda

Milan, , Italy

Site Status RECRUITING

Ospedale San Raffaele IRCCS

Milan, , Italy

Site Status RECRUITING

Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale

Napoli, , Italy

Site Status RECRUITING

Ospedale San Francesco

Nuoro, , Italy

Site Status TERMINATED

Azienda Ospedaliera San Giovanni - Addolorata

Roma, , Italy

Site Status SUSPENDED

Countries

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Italy

Central Contacts

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Igor Monsellato, MD

Role: CONTACT

+390131206506

Facility Contacts

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Igor Monsellato, Md, PhD

Role: primary

Davide Cavaliere, MD

Role: primary

Enzo Mammano, MD

Role: primary

Giacomo Ruffo

Role: primary

Roberto Perinotti, MD

Role: primary

Marco LF Bonù, MD

Role: primary

Gianluca Baiocchi, Prof

Role: primary

Federico Perna, MD

Role: primary

Luigi Boni, FACS

Role: primary

Ugo Elmore

Role: primary

Paolo Delrio, Prof

Role: primary

References

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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.

Reference Type RESULT
PMID: 15496622 (View on PubMed)

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.

Reference Type RESULT
PMID: 24263329 (View on PubMed)

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.

Reference Type RESULT
PMID: 28190762 (View on PubMed)

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.

Reference Type RESULT
PMID: 28374169 (View on PubMed)

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.

Reference Type RESULT
PMID: 27432930 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31842784 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1/18

Identifier Type: -

Identifier Source: org_study_id

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