Timing to Minimally Invasive Surgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer

Study Overview
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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.

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

Conditions
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Rectal Cancer

Intervention / Treatment
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* Procedure: Surgery after 8 weeks from chemoradiation treatment
* Procedure: Surgery after 12 weeks from chemoradiation treatment


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Interval Time Arm<br>Minimally invasive surgery after 8 weeks from chemoradiation treatment | Procedure: Surgery after 8 weeks from chemoradiation treatment<br>* Minimally invasive surgery after 8 weeks from chemoradiation treatment<br>|
| Active Comparator: Delayed Interval Time Arm<br>Minimally invasive surgery after 12 weeks from chemoradiation treatment | Procedure: Surgery after 12 weeks from chemoradiation treatment<br>* Minimally invasive surgery after 12 weeks from chemoradiation treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response (pCR) | 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 | Disease Free survival | 5 years | 
| OS | Overall Survival | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, robotic rectal cancer resection, minimally invasive surgery, Colorectal Cancer, chemoradiation treatment rectal cancer