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Trial registered on ANZCTR


Registration number
ACTRN12612000835842
Ethics application status
Approved
Date submitted
4/08/2012
Date registered
8/08/2012
Date last updated
28/05/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Proctectomy with sphincter preservation in very low rectal cancer that traditionally need abdominoperineal resection with permanent colostomy
Scientific title
Effect of changing decision of abdominoperineal resection to sphincter preserving technique in very low rectal cancer after downstaging by neoadjuvant chemoradiation on recurrence and survival
Secondary ID [1] 280974 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low rectal cancer 287086 0
Condition category
Condition code
Surgery 287414 287414 0 0
Surgical techniques
Cancer 287434 287434 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with stage II and III low rectal cancer less than 5 cm from anal verge usually need abdominoperineal resection. Preoperative neoadjuvant chemoradiation(54 grays of radiation divided over 5 weeks with chemotherapy by intravenous 5-fu and leucovorin 1 day a week for 5 weeks; 5-FU 425 mg/m2 plus LV 45 mg ) helps in tumor downstaging and downsizing that might help to resect the tumor with safety margin without removing the anal sphincters. Patients with T3, T4 low rectal tumors 5 cm or less from anal verge receive neoadjuvant preoperative chemoradiation. Patient assessment is done 8 weeks after the end of chemoradiation by digital rectal examination and endorectal ultrasound. If there is tumor downsizing that leaves safety margin above the anal sphincters, , then very low anterior resection with coloanal anastomosis is performed (120-180 minutes) . If no sufficient safety margin, intersphincteric resection (120-180 minutes) with coloanal anastomosis is done if the external anal sphincter is not involved (yT2), if the external sphincter was involved so abdominoperineal resection is done and excluded from study.
Intervention code [1] 285420 0
Treatment: Surgery
Intervention code [2] 285432 0
Treatment: Drugs
Comparator / control treatment
nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287677 0
Perioperative morbidity assesed by clinical examination of the abdomen to diagnose wound problems, chest x ray and Ultrasound abdomen
Timepoint [1] 287677 0
1-30 days postoperative
Primary outcome [2] 287678 0
Perioperative mortailty
Timepoint [2] 287678 0
1-30 days postoperative
Primary outcome [3] 287679 0
Tumor recurrence assessed by clinical examination and abdominal CT scan
Timepoint [3] 287679 0
every 6 months postoperative for 2 years
Secondary outcome [1] 298621 0
Morbidity and mortality after salvage surgery in case of recurrence by clinical examination of the abdomen to diagnose wound problems, chest x ray and Ultrasound abdomen
Timepoint [1] 298621 0
1-30 days postoperative after salvage surgery
Secondary outcome [2] 298654 0
Continence assessed by wexner score
Timepoint [2] 298654 0
6 months and 1 year postoperative

Eligibility
Key inclusion criteria
Adult male or female 18-80 years
low rectal tumor, 5 cm or less from anal verge
Stage II or III
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Stage IV tumors
fecal incontinence assessed by wexner score

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4460 0
Egypt
State/province [1] 4460 0

Funding & Sponsors
Funding source category [1] 285756 0
Self funded/Unfunded
Name [1] 285756 0
Address [1] 285756 0
Country [1] 285756 0
Egypt
Primary sponsor type
Individual
Name
Khaled Madbouly
Address
Kolet el teb street, Azarita, Faculty of medicine, university of alexandria, Alexandria, 21321, egypt
Country
Egypt
Secondary sponsor category [1] 284586 0
None
Name [1] 284586 0
Address [1] 284586 0
Country [1] 284586 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287769 0
Ethics Committee, University of Alexandria
Ethics committee address [1] 287769 0
Kolet el teb street, Azarita, Faculty of medicine, university of alexandria, Alexandria, 21321, egypt
Ethics committee country [1] 287769 0
Egypt
Date submitted for ethics approval [1] 287769 0
Approval date [1] 287769 0
Ethics approval number [1] 287769 0

Summary
Brief summary
Background:
Multimodality treatment of rectal cancer, with the combination of radiation therapy, chemotherapy, and surgery has become the preferred approach to locally advanced rectal cancer.The considerably high local recurrence rates observed after radical
surgery alone has led to the use and recommendation for additional therapy either before or after surgery for T3/T4 or N1 tumors. In this setting, to avoid overtreatment
of patients with early-stage disease, preoperative treatment with radiation therapy with or without concomitant chemotherapy requires optimal radiological staging because
there is no pathologic confirmation of exact TNM parameters. However, there is a theoretic benefit of exposing unscarred tissue with optimal oxygen delivery to both radiation
and chemotherapy as opposed to postoperative treatment. The results from randomized controlled trials suggest that the neoadjuvant approach seems to be superior for
local disease control, even in the setting of appropriate surgical technique (total mesorectal excision). The use of neoadjuvant chemoradiation therapy (CRT) has resulted in
additional benefits such as reduced toxicity rates, significant tumor downsizing and downstaging, better chance of sphincter preservation, and improved functional results
(compared with postoperative CRT). In a multicenter study of patients undergoing neoadjuvant CRT for clinically stage II disease (staged by either endorectal ultrasound
or magnetic resonance imaging), more than 20% of the patients staged as N0 were found to harbor lymph node metastases in their tumors on pathologic examination.
Considering that these patients underwent neoadjuvant CRT, even greater rates of nodal disease underestimation might be expected. Radical surgery with total mesorectal excision remains the mainstay of treatment of distal rectal cancer and is considered by many to be necessary regardless of tumor
response to neoadjuvant CRT. However, it has been associated with high rates of immediate morbidity and mortality. With very low tumors, abdominoperineal resection sometimes is necessary with the result of permenant colostomy and disturbance of the quality of life. Up till now, many authors believe that the decision of surgery should be set before any change in the tumor by neoadjuvant chemoradiation, however haber-gama who concluded that with complete pathologic response and restrict criteria, it is safe just to follow up the patient without surgery. Changing decision to sphincter preserving technique in patients who have good response to neoadjuvant chemoradiation with downsizing and downstaging is still contraversail.

Aim of the work:
To study the safety of changing decision from abdominoperineal resection to sphincter preserving technique in low rectal tumors after downsizing be neoadjuvant chemoradiation. Aspects of safety will include periperative morbidity, mortality, continence, recurrences and results of salvage surgery after recurrence.

Study design: Patients with stage II and III low rectal cancer less than 5 cm from anal verge usually need abdominoperineal resection. Preoperative neoadjuvant chemoradiation helps in tumor downstaging and downsizing that might help to resect the tumor with safety margin without removing the anal sphincters. Patients with T3, T4 low rectal tumors 5 cm or less from anal verge receive neoadjuvant preoperative chemoradiation. Patient assessment is done 8 weeks after the end of chemoradiation by digital rectal examination and endorectal ultrasound. If there is tumor downsizing that leaves safety margin above the anal sphincters, , then very low anterior resection with coloanal anastomosis is performed. If no sufficient safety margin, intersphincteric resection with coloanal anastomosis is done if the external anal sphincter is not involved (yT2), if the external sphincter was involved so abdominoperineal resection is done.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34538 0
A/Prof Khaled Madbouly
Address 34538 0
Faculty of Medicine, University of Alexandria. Kolet el teb Street, Azarita, Alexandria. 21321
Country 34538 0
Egypt
Phone 34538 0
+2034802375
Fax 34538 0
Email 34538 0
khaled.madbouly@alexmed.edu.eg
Contact person for public queries
Name 17785 0
A/Prof Khaled Madbouly
Address 17785 0
Kolet el teb street, Azarita, Faculty of medicine, university of alexandria, Alexandria, 21321, egypt
Country 17785 0
Egypt
Phone 17785 0
+20 34802375
Fax 17785 0
Email 17785 0
khaled.madbouly@alexmed.edu.eg
Contact person for scientific queries
Name 8713 0
A/Prof Khaled Madbouly
Address 8713 0
Kolet el teb street, Azarita, Faculty of medicine, university of alexandria, Alexandria, 21321, egypt
Country 8713 0
Egypt
Phone 8713 0
+20 34802375
Fax 8713 0
Email 8713 0
khaled.madbouly@alexmed.edu.eg

No information has been provided regarding IPD availability
Summary results
No Results