Clinical trial NCT03465982: Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer
Official title: Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer: a Multicenter Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Keywords: rectal cancer
robotic rectal cancer resection
minimally invasive surgery
Colorectal Cancer
chemoradiation treatment rectal cancer
Lead sponsor: Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
Sponsor class: OTHER
First posted: 2018-03-15
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: pathologic complete response (pCR)
timeFrame: 8-12 weeks
Secondary outcomes:
measure: DFS
timeFrame: 5 years
measure: OS
timeFrame: 5 years
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: SS. Antonio e Biagio e Cesare Arrigo Hospital
state: AL
city: Forlì
country: Italy
facility: Ospedale Gian Battista Morgagni - Luigi Pierantoni
state: Forlì-Cesena
city: Camposampiero
country: Italy
facility: Ospedale Civile Pietro Cosma
state: Padua
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore
state: Verona
city: Acquaviva Delle Fonti
country: Italy
facility: Ente Ecclesiastico ospedale generale Regionale Miulli
city: Biella
country: Italy
facility: Ospedale degli Infermi
city: Brescia
country: Italy
facility: Istituto del Radio Olindo Alberti, Spedali Civili di Brescia
city: Cremona
country: Italy
facility: ASST Ospedale di Cremona
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico Fondazione Ca' Granda
city: Milano
country: Italy
facility: Ospedale San Raffaele IRCCS
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale
city: Nuoro
country: Italy
facility: Ospedale San Francesco
city: Roma
country: Italy
facility: Azienda Ospedaliera San Giovanni - Addolorata
Study officials:
References:
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.
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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.