Timing for Rectal Surgery After Chemoradiotherapy (ST812)

Timing for Rectal Surgery After ChST

The aim of this study is to determine whether greater rectal cancer downstaging and regression occurs when surgery is delayed to 12 weeks after completion of radiotherapy/chemotherapy compared to 8 weeks.

Hypothesis: Greater down-staging and tumor regression is observed when surgery is delayed to 12 weeks after completion of chemoradiotherapy compared to 8 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: Surgery after 12 weeks of delay after chemoradiotherapy.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Lithuania
  • Vilnius, Lithuania, 08406
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Over 18 years old
• Eastern Cooperative Oncology Group (ECOG) 0-1,
• American Society of Anesthesiologists' (ASA) score I-III
• Histological confirmation of adenocarcinoma of rectum
• T3 or T4 N0, T any N positive cancer on MRI, without metastasis on CT scan
• Undergoing preoperative radiotherapy/ chemotherapy
• Curative total mesorectal excision intended
• Written informed consent
• Patients undergoing preoperative radiotherapy should not be excluded

Exclusion Criteria:

• Patients with distant metastasis
• T1 or T2, N0 cancer on MRI
• Rectal cancer 12 cm above the dentate line
• Contraindications to MRI
• Patients previously treated of pelvic organ cancer
• Medical or psychiatric conditions that compromise the patients ability to give informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1; The cancer surgery is practice 8 weeks after neoadjuvant chemoradiotherapy
Experimental: Group 2; The cancer surgery will be performed in 12 weeks after neoadjuvant chemoradiotherapy	Procedure: Surgery after 12 weeks of delay after chemoradiotherapy.; Surgery consists oncologic resection of the rectal cancer with total excision of the mesorectum after 12 weeks of delay after the end of chemoradiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete pathologic response assessed by pathologist Dworak scale	Dworak scale assesses the response: 0. No regression; 1. Predominantly tumor with significant fibrosis and/or vasculopathy; 2. Predominantly fibrosis with scattered tumor cells (slightly recognizable histologically); 3. Only scattered tumor cells in the space of fibrosis with/without acellular mucin; 4. No vital tumor cells detectable	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response assessed using MRi	Rates of clinical response to chemoradiotherapy before surgery, comparison between the two groups	8 weeks (2 months)
Pathological response assessed by pathologist using Dworak scale	Dworak scale assesses the response: 0. No regression; 1. Predominantly tumor with significant fibrosis and/or vasculopathy; 2. Predominantly fibrosis with scattered tumor cells (slightly recognizable histologically); 3. Only scattered tumor cells in the space of fibrosis with/without acellular mucin; 4. No vital tumor cells detectable	6 months
Incidence of Treatment-Emergent Adverse Events as assessed by Clavien-Dindo scale	Rates of operative morbidity at 30 days, comparison between the two groups. Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside. Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusionsand total parenteral nutritionare also included. Grade III Requiring surgical, endoscopic or radiological intervention; IIIa Intervention not under general anesthesia; IIIb Intervention under general anesthesia Grade IV Life-threatening complication (including CNS complications)* requiring IC/ICU-management; IVa single organ dysfunction (including dialysis); IVb multiorgan dysfunction	30 days
Incidence of Mortality assessed by Clavien-Dindo scale	Rates of operative mortality at 30 days, comparison between the two groups. Grade V Death of a patient	30 days
Total mesorectal excision (TME) quality assessed by TME completeness scale (by P.Quircke)	Quality of mesorectum resection assessed by TME completeness scale: Mesorectal resection (MRR)/good/complete: intact mesorectum and smooth mesorectal surface with only minor irregularities; no defects deeper than 5 mm; no coning of the specimen towards the distal margin; and smooth macro-circular resection margin (CRM) on slicing.; Intramesorectal resection (IMR)/intermediate/nearly complete: intermediate bulk of the mesorectum with an irregular surface; a defect deeper than 5 mm, and no visible muscularis propria other than inserted levator; intermediate coning; intermediate irregularity of macro-CRM on slicing.; Muscularis propria resection (MPR)/poor/incomplete: small bulk of the mesorectum with a very irregular surface; defect down to the muscularis propria; severe coning; severe irregularity of macro-CRM on slicing.	8-12 weeks
Distant recurrence assessed by CT scan	Distant recurrence rates, comparison between the two groups	5 years
Local recurrence assessed by CT scan/MRI/endoscopy	Local recurrence rates, comparison between the two groups	5 years
Oncological outcome - overall survival	Overall survival rates, comparison between the two groups	5 years
Oncological outcome - disease-free survival	Disease-free survival rates, comparison between the two groups	5 years
Radiotherapy skin toxicity assessed by EORTC scale	Radiotherapy related toxicity rates: skin reactions will be assessed using EORTC radiotherapy toxicity scale: Skin Grade 1 follicular, faint or dull erythema / epilation / dry desquamation / decreased sweating; Grade 2 tender or bright erythema, patchy moist desquamation / moderate edema; Grade 3 confluent, moist desquamation other than skin folds, pitting edema; Grade 4 - ulceration, hemorrhage, necrosis	5 years
Radiotherapy toxicity assessed by EORTC scale	Radiotherapy related toxicity rates: gastrointestinal reactions will be assessed using EORTC radiotherapy toxicity scale: Grade 1 increased frequency or change in quality of bowel habits not requiring medication / rectal discomfort not requiring analgesics; Grade 2 diarrhea requiring parasympatholytic drugs (e.g. Lomotil) / mucous discharge not necessitating sanitary pads / rectal or abdominal pain requiring analgesics; Grade 3 diarrhea requiring parenteral support / severe mucous or blood discharge necessitating sanitary pads / abdominal distention (flat plate radiograph demonstrates distended bowel loops); Grade 4 acute or subacute obstruction, fistula or perforation; GI bleeding requiring transfusion; abdominal pain or tenesmus requiring tube decompression or bowel diversion	5 years
Quality of Life assessed by Low anterior resection syndrome score	The Low anterior resection syndrome score (LARS) score consists of five items concerning the following: incontinence for flatus, incontinence for liquid stool, frequency of bowel movements, clustering of stools, and urgency. Each symptom of bowel dysfunction is weighed according to its impact on the quality of life. The calculated score ranges from 0 to 42, with a score of 0-20 representing no ARS, a score of 21-29 representing minor ARS, and a score of 30-42 representing major ARS.	1 year
Immune response assessed	We have assessed the immune response before chemoradiotherapy and 8 weeks following the treatment. IL1B, IL6, IL8, IL10, IL2R, TNF alfa are assessed and will be correlated with the response to treatment.	1 year
Urinary catheter removal timing	All the patients will have there urinary catheters removed on day 1. Some patients will get Urorec (adrenomimetic for prevention of urinary retention). The patients will be randomized 2:1	3 months

Collaborators and Investigators

• Sponsor: National Cancer Institute, Lithuania
• Investigators: Principal Investigator: Audrius Dulskas, MD, PhD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Rectal cancer; Chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: ST812

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No