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Trial registered on ANZCTR


Registration number
ACTRN12609000663257
Ethics application status
Approved
Date submitted
15/07/2009
Date registered
5/08/2009
Date last updated
13/11/2018
Date data sharing statement initially provided
13/11/2018
Date results information initially provided
13/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A La CaRT: Australasian Laparoscopic Cancer of the Rectum Trial
A phase III prospective randomised trial comparing laparoscopic-assisted resection
versus open resection for rectal cancer
Scientific title
A La CaRT: Australasian Laparoscopic Cancer of the Rectum Trial
A phase III prospective randomised trial comparing laparoscopic-assisted resection
versus open resection for rectal cancer
Secondary ID [1] 253296 0
A La CaRT
Universal Trial Number (UTN)
Trial acronym
A La CaRT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The study compares two types of surgery for rectal cancer stage T 0-3, N 0-1, M 0-laparoscopic-assisted resection versus open resection 243457 0
Condition category
Condition code
Cancer 239757 239757 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two types of surgery are currently available in the treatment of rectal cancer: open laparotomy and rectal resection and laparoscopic-assisted rectal resection.

While open laparotomy (an incision into the abdomen) and surgical resection is currently the standard of care for rectal cancer, laparoscopic-assisted resection (“key-hole” surgery to resect the tumour, performed under the guidance of a video camera) has emerged as a new treatment option for rectal cancer. This technique achieves removal of the rectal tumour with minimally invasive surgery, and potentially achieves better recovery and shorter stays in hospital post-operatively.
Patients will be randomised to receive one of the two surgical treatments to remove the primary rectal cancer - i.e. Open Laparotomy and Rectal Resection or Laparoscopic-assisted Rectal Resection.
Intervention code [1] 237072 0
Treatment: Surgery
Comparator / control treatment
The purpose of the A La CaRT study is to compare these two types of surgery and to
determine whether the new technique of laparoscopic-assisted resection is as safe and effective as the current standard of open laparotomy and resection in the treatment of rectal cancer.

This study will also determine whether disease recurrence rates are improved and whether patients with rectal cancer benefit through improved short and long term recovery and overall quality of life.
Control group
Active

Outcomes
Primary outcome [1] 240521 0
To determine whether laparoscopic-assisted resection is not inferior to open rectal resection as a safe, effective oncologic approach to rectal cancer.
Timepoint [1] 240521 0
Pre-operative staging and evaluation of disease will be determined by Computerised Tomography (CT) scan, and pelvic Magnetic Resonance Imaging) MRI or CT scan and Endorectal ultrasound. Pathology specimens obtained at surgery will be reviewed by a Pathology Review Committee to assess a composite of oncologic parameters which must be met for surgical resection to be successful. These parameters which form the primary endpoint are:
Circumferential margin greater than or equal to 1mm
Distal resected margin greater than or equal to 2cm (or greater than or equal to 1cm with clear frozen section in the low rectum)
Completeness of total mesorectal excision (TME)
Secondary outcome [1] 257075 0
To determine whether laparoscopic resection for rectal cancer is not inferior to open resection from a patient related benefit perspective, based on morbidity, mortality associated with surgery, disease-free survival and disease recurrence and quality of life.
Timepoint [1] 257075 0
Pre-operative assessment of clinical status and baseline quality of life questionnaire instruments will be completed within 6 weeks prior to surgery. Follow up visits take place at day 3 and day 14 post surgery, and then at 4-6 weeks, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months and annually at 3,4,and 5 years. Patient morbidity/mortality associated with surgical intervention data is to be collected, disease-free survival and local pelvic recurrence is assessed at 2 years, overall survival is assessed at 5 years, and quality of life assessment is followed to one year.

Eligibility
Key inclusion criteria
a. Histological diagnosis of adenocarcinoma of the rectum (<15cm from the anal verge as measured by rigid sigmoidoscopy).
b. T 1-3 N0 M0, T1-3 N1 M0 or T1-3 N0-1 M1 disease as determined by pre-treatment CT scans and pelvic MRI (or endorectal ultrasound if MRI contraindicated)
i. For evaluation of pelvis: MRI +/-ERUS; or ERUS alone if MRI contra-indicated
ii. For evaluation of abdomen, liver: CT
iii. For evaluation of chest: either CT or CXR

c. For patients with T3 or N1 disease, completion of pre-operative 5FU-based chemotherapy and/or radiation therapy. Capecitabine may be substituted for 5FU.
d. Age = 18 years.
e. ECOG Performance Status: 0, 1 or 2.
f. Written informed consent.
g. Life expectancy of at least 12 weeks.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a.Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol.
b.Pregnancy or breast feeding.
c.Any uncontrolled concurrent medical condition.
d.Any co-morbid disease that would increase risk of morbidity.
e.Participation in any investigational drug study within the previous 4 weeks.
f.Evidence of T4 disease extending to circumferential margin of rectum or invading adjacent organs.
g.Evidence of systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude surgery, or other severe incapacitating disease, i.e. as per the grading system of the American Society of Anaesthesiologists (ASA), ASA IV (a patient with severe systemic disease that is a constant threat to life) or ASA V (a moribund patient who is not expected to survive without the operation).
h.History of conditions that would preclude use of a laparoscopic approach (e.g. multiple previous major laparotomies, severe adhesions).
i.Concurrent or previous invasive pelvic malignancy (cervical, uterine and rectal) within five years prior to registration.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
On confirmation of eligibility, patients will be recruited through the hospital, clinic or surgeons' rooms at each site. Sites will fax randomisation data to the central coordinating body, the National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC). Only authorised staff at the NHMRC CTC are eligible to access the randomisation system. Upon verification of site accreditation, patient eligibility, that documentation is correct and complete, a check is performed to ensure that patient duplication will not occur, before allocation to either treatment arm is performed. This allocation is by an electronic randomisation system which generates patient study ID and treatment arm.
Patients will be randomised to either open laparotomy and rectal resection or laparoscopic-assisted rectal resection.
Confirmation of randomisation, patient ID and treatment arm is faxed by the NHMRC CTC to the investigator at the study site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study numbers are assigned by simple randomisation by using a randomisation table created by computer software (i.e. computerised sequence generation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The NHMRC Clinical Trials Centre/Australian Gastro-Intestinal Trials Group (AGITG) Coordinating Centre will validate all investigator and site credentials prior to randomisation. Upon confirmation of eligibility, patients will be stratified by site of primary tumour (high, middle or low rectum), registering surgeon, planned operative procedure (low anterior resection or abdominoperineal resection), body mass index (BMI) BMI <30 vs >30, whether receiving pre or post-operative radiotherapy and according to the metastases stage (M0 or M1).
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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 in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA
Recruitment outside Australia
Country [1] 1880 0
New Zealand
State/province [1] 1880 0
Auckland, Christchurch

Funding & Sponsors
Funding source category [1] 237450 0
Other Collaborative groups
Name [1] 237450 0
Colorectal Surgical Society of Australia and New Zealand (CSSANZ)
Address [1] 237450 0
Level 2, 4 Cato St,
Hawthorn,
Victoria, 3122
Country [1] 237450 0
Australia
Funding source category [2] 258213 0
Government body
Name [2] 258213 0
NHRMC / Cancer Australia
Address [2] 258213 0
Level 6, G02
Jane Foss Russell Building
University of Sydney NSW 2006
Country [2] 258213 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian Gastro-Intestinal Trials Group (AGITG)
Address
AGITG Coordinating Centre
NHMRC Clinical Trials Centre
University of Sydney
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 236939 0
None
Name [1] 236939 0
Address [1] 236939 0
Country [1] 236939 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239455 0
Cancer Institute NSW Clinical Research Ethics Committee
Ethics committee address [1] 239455 0
Clinical Research Ethics Committee
Cancer Insitute NSW
PO Box 41
Alexandria
NSW 1435
Ethics committee country [1] 239455 0
Australia
Date submitted for ethics approval [1] 239455 0
29/06/2009
Approval date [1] 239455 0
02/09/2009
Ethics approval number [1] 239455 0
EC00414

Summary
Brief summary
This study compares surgery using a laparoscope (keyhole surgery) compared with open surgery in treating colorectal (bowel) cancer.
You can join this study if you have been diagnosed with primary cancer of the rectum or lower bowel (stage T 1-3 N 0-1 M 0-1) that requires surgery.

Trial participants will be randomly divided into two groups. One group will receive surgery using a laparoscope (keyhole surgery) while the other will receive the standard open surgery. Patients will be assessed 6 weeks prior to surgery, with follow up checks at day 3 and day 14 post surgery, and then at 4–6 weeks, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months and annually at 3, 4 and 5 years.
Surgical resection of the tumour is the most important treatment for rectal cancer. Laparoscopic-assisted techniques allow the tumour to be removed with smaller incisions, and less invasive surgery.
This study aims to determine whether these new techniques offer a safe and viable alternative to standard surgery.

The primary aim of this study will be to determine whether laparoscopic-assisted resection of rectal cancer is non-inferior (or equivalent) in safety and efficacy to the open technique of laparotomy and surgical resection.
The secondary aim of the study will be to determine whether laparoscopic-assisted rectal resection is equivalent to open rectal resection in providing comparable recovery outcomes and in terms of disease recurrence and survival, and quality of life.
Trial website
Australasian Gastro-Intestinal Trials Group (AGITG) at www.gicancer.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29892 0
A/Prof Andrew Stevenson
Address 29892 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown, NSW, 1450, Australia
Country 29892 0
Australia
Phone 29892 0
+61 2 9562 5000
Fax 29892 0
Email 29892 0
alacart@ctc.usyd.edu.au
Contact person for public queries
Name 13139 0
Ms A La CaRT Trial Coordinator
Address 13139 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown, NSW, 1450, Australia
Country 13139 0
Australia
Phone 13139 0
+61 2 9562 5000
Fax 13139 0
+61 (2) 9562 5094
Email 13139 0
alacart@ctc.usyd.edu.au
Contact person for scientific queries
Name 4067 0
Ms A La CaRT Trial Coordinator
Address 4067 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown, NSW, 1450, Australia
Country 4067 0
Australia
Phone 4067 0
+61 2 9562 5000
Fax 4067 0
+61 (2) 9562 5094
Email 4067 0
alacart@ctc.usyd.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not according to the protocol
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 216 0
JAMA, 6 October 2015, Volume 314, Number 13
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
This was a non-inferiority trial. Therefore, it was not testing whether the new treatment (laparoscopic surgery) was better, but whether it was no worse than the traditional treatment (open surgery). The trial showed that non-inferiority was not ruled out.
That is, open surgery may be better. Surgery was successful in 82% of the laparoscopic surgery group and 89% of the open surgery group. The margin around the tumour was clear in 93% of patients in the laparoscopy group and 97% of those having open surgery. Overall, the rate of successful surgery was high, especially as a quarter of the patients were obese and many overweight, which makes the operation more challenging.