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Trial registered on ANZCTR


Registration number
ACTRN12614001195640
Ethics application status
Approved
Date submitted
7/08/2014
Date registered
13/11/2014
Date last updated
25/09/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
RELY-Resection of colorectal liver metastases with or without routine hilar lymphadenectomy - A Randomized Controlled Trial
Scientific title
Effect of resection of colorectal liver metastases with or without routine hilar lymphadenectomy on disease recurrence within 2 years
Secondary ID [1] 285117 0
NCT01073358
Universal Trial Number (UTN)
U1111-1160-1033
Trial acronym
RELY study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
colorectal liver metastases 292675 0
Condition category
Condition code
Cancer 292986 292986 0 0
Liver
Cancer 293082 293082 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group A: Resection of colorectal liver metastases without routine hilar lymphadenectomy. However, patients with macroscopically enlarged lymph nodes undergo lymphadenectomy in accordance with current guidelines at the Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden. These patients will be analyzed in the intention-to-treat population.

Group B: Routine hilar lymphadenectomy
First, exploration of the abdomen and intraoperative ultrasound are performed to assess the extent of intrahepatic and potential extrahepatic disease and to confirm resectability. Hilar lymphadenectomy is performed before actual resection of the colorectal liver metastases. Following cholecystectomy in a fundus-first fashion, hilar lymphadenectomy is carried out including defined groups of lymph nodes (nomenclature of the lymph nodes according to the Japanese classification of gastric cancer). The groups of lymph nodes at the following sites will be resected : Common hepatic artery, Coeliac trunk, duodenal ligament, hepatic artery, Hepatoduodenal ligament, portal vein/bile duct.
The duration of each procedure is approximately 200 minutes
Intervention code [1] 289966 0
Treatment: Surgery
Comparator / control treatment
Group A: No routine hilar lymphadenectomy
Resection of colorectal liver metastases without routine hilar lymphadenectomy. However, patients with macroscopically enlarged lymph nodes undergo lymphadenectomy in accordance with current guidelines at the Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden. These patients will be analyzed in the intention-to-treat population.
Control group
Active

Outcomes
Primary outcome [1] 292847 0
Frequency of disease recurrence within 24 months in patients undergoing resection of CRC liver metastases with routine hilar lymphadenectomy compared to no hilar lymphadenectomy.
A CRF data form is used to catch this information.
Timepoint [1] 292847 0
24 months assessed by course of disease including adjuvant chemotherapy and disease recurrence
Primary outcome [2] 293512 0
Quality of life patient questionnaire is assessed using the validated EuroQoL 5 questionnaire completed by the patient
Timepoint [2] 293512 0
Assessed preoperatively and three months after surgery
Secondary outcome [1] 309798 0
Intraoperative blood loss [mL]
Intraoperative blood loss will be measured according to the blood collected in the suction containers from the timepoint of skin incision until closure of the skin. Spilling water and ascites will be subtracted. Furthermore, swabs will be squeezed and their content will also be sucked and added to the fluid collected in the suction containers. A CRF data form is used to catch this information.
Timepoint [1] 309798 0
day of surgery
Secondary outcome [2] 309989 0
Time to death (Overall survival)
Time from date of resection of colorectal liver metastases to date of death due to colorectal cancer
Timepoint [2] 309989 0
24 months
Secondary outcome [3] 309990 0
Number of patients requiring blood transfusions
Administration of blood transfusions is documented for the intraoperative and postoperative period until 48 hours postoperatively. Documentation includes number of patients who received blood transfusions as well as amount of transfused packed red blood cells (PRBC) [units].
A CRF data form is used to catch this information.
Timepoint [3] 309990 0
48 hours
Secondary outcome [4] 309991 0
Extent of hepatic resection assessed by the surgeon. A CRF data form is used to catch this information.
Timepoint [4] 309991 0
Assessed directly after the surgical procedure.
Secondary outcome [5] 311215 0
surgical techniques used by the surgeon during surgery are assessed by the surgeon. This includes whether inflow control was performed or any other vascular clamping. A CRF data form is used to catch this information.
Timepoint [5] 311215 0
Assessed and documented the day of the operation
Secondary outcome [6] 311216 0
operative measures are assessed and documented including the operation date, time of first incision, time of last suture, duration of the procedure and the total blood loss. A CRF data form is used to catch this information.
Timepoint [6] 311216 0
Assessed and documented during the procedure

Eligibility
Key inclusion criteria
Patients scheduled for resection of colorectal cancer liver metastases. Patients undergoing simultanous resection of the primary tumor together with liver metastases may also be enrolled in the trial
Patients scheduled for curative (R0) resection
No evidence of extrahepatic disease
No history of previous hilar lymphadenectomy
Age equal or greater than 18 years
Written Informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Expected lack of compliance
Impaired mental state or language problems
History of another primary cancer, except:
Curatively treated in situ cervical cancer or curatively resected non-melanoma skin cancer
Other primary solid tumour curatively treated with no known active disease present and no treatment administered for up to 5 years prior to randomisation

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)
Randomization is carried out using opaque and sealed envelopes that are consecutively numbered.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization will be performed for each centre to achieve equal group sizes per centre. The details of randomization will be kept safe and confidential.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical methods are used to assess the quality of data, homogeneity of treatment groups, endpoints and safety of the two intervention groups. The confirmatory analysis is performed on the basis of an intention-to-treat (ITT) population and with respect to ITT principles.
Categorical data are summarized by means of absolute and relative frequencies (count and percent). Continuous data are presented by means of the following summary statistics: the number of observations, arithmetic mean, standard deviation, minimum, median and maximum. Wherever appropriate, data are visualized by box-whisker plots or histograms. The primary efficacy endpoint is amount of intraoperative blood loss. A confirmatory intention to treat analysis (2-sided test), including all patients as randomized, is performed on the disease recurrence rates between the two groups. Binary logistic regression analysis is used to detect possible treatment differences with disease recurrence as dependent variable, age at surgery, MSKCC score and adjuvant chemotherapy as covariates. The sample size calculation is based on a two-sided test, and it can be assumed that evaluation with logistic regression analysis has the same or even higher power.
Secondary endpoints will be analyzed in an exploratory way, using appropriate statistical methods based on the underlying distribution of the data. Sensitivity analysis will be conducted including per-protocol population and center as additional covariates in the logistic regression model.
Sample size calculation
The sample size is based on the primary outcome parameter and the primary analysis. Clinical studies on patients undergoing resection of colorectal liver metastases showed recurrence rates of 50% at two years. To detect a clinically relevant absolute difference in reduction of disease recurrence of 20% with significance =5% and a power of 1=80% n=186 patients have to be randomized in the study (n=93 patients per group). Considering a drop-out rate of 20% (perioperative mortality, unresectable disease, loss to follow-up) mortality within 2 years due to underlying disease the total sample size accounts for n=224 patients

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/08/2014
Actual
16/09/2014
Date of last participant enrolment
Anticipated
14/03/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
224
Accrual to date
180
Final
Recruitment outside Australia
Country [1] 6281 0
New Zealand
State/province [1] 6281 0
Auckland
Country [2] 6282 0
Germany
State/province [2] 6282 0
Heidelberg
Country [3] 6298 0
Germany
State/province [3] 6298 0
Dresden
Country [4] 6299 0
Germany
State/province [4] 6299 0
Frankfurt

Funding & Sponsors
Funding source category [1] 289724 0
Hospital
Name [1] 289724 0
Upper GI research funds. Three Harbours Trust. North Shore Hospital
Country [1] 289724 0
New Zealand
Primary sponsor type
Individual
Name
Juergen Weitz, MD, MSc
Address
Department of Visceral, Thoracic and Vascular Surgery
University Hospital Carl Gustav Carus
University of Technology Dresden
Fetscherstrase 74, 01307 Dresden, Germany
Country
Germany
Secondary sponsor category [1] 288419 0
None
Name [1] 288419 0
Address [1] 288419 0
Country [1] 288419 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291463 0
Health and Disability Ethics Committees. Northern B Health and Disability Ethics Committee.
Ethics committee address [1] 291463 0
Health and Disability Ethics Committees
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 291463 0
New Zealand
Date submitted for ethics approval [1] 291463 0
13/06/2014
Approval date [1] 291463 0
09/07/2014
Ethics approval number [1] 291463 0
14/NTB/77

Summary
Brief summary
This trial is designed to show that routine hilar lymphadenectomy compared to no routine lymphadenectomy improves the rate of disease recurrence within 2 years after surgery in patients undergoing resection of CRC liver metastases
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 152 152 0 0
/AnzctrAttachments/366863-RELY_Study Protocol.doc
Attachments [2] 153 153 0 0
/AnzctrAttachments/366863-VERSION2 CLEAN PARTICIPANT INFORMATION SHEET(FINAL).docx
Attachments [3] 154 154 0 0
/AnzctrAttachments/366863-HDEC_Letter_14NTB77_Approved_FULL_Application_with_Non-Standard_Conditions[1].pdf
Attachments [4] 2082 2082 0 0
/AnzctrAttachments/366863-HDEC Letter 14NTB77AM04 Approved Progress Report.pdf (Other)

Contacts
Principal investigator
Name 50510 0
A/Prof Jonathan Koea
Address 50510 0
North shore Hospital.
42, Shakespeare Road. Takapuna. Auckland 0740
Country 50510 0
New Zealand
Phone 50510 0
+64 09 4868920 ext: 7233
Fax 50510 0
Email 50510 0
[email protected]
Contact person for public queries
Name 50511 0
Sherry Nisbet
Address 50511 0
North shore Hospital. 42, Shakespeare Road. Takapuna. Auckland 0740
Country 50511 0
New Zealand
Phone 50511 0
+64 094868920. ext:7233
Fax 50511 0
Email 50511 0
[email protected]
Contact person for scientific queries
Name 50512 0
Juergen Weitz, MD, MSc
Address 50512 0
Department of Visceral, Thoracic and Vascular Surgery
University Hospital Carl Gustav Carus
University of Technology Dresden
Fetscherstrase 74, 01307 Dresden, Germany
Country 50512 0
Germany
Phone 50512 0
+49-(0)351-458-2742
Fax 50512 0
+49-(0)351-458-4395
Email 50512 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23349Other  [email protected]
23824Other    an overall report

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.