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Trial registered on ANZCTR


Registration number
ACTRN12617001560381
Ethics application status
Approved
Date submitted
7/11/2017
Date registered
15/11/2017
Date last updated
17/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Use of circulating tumour DNA (ctDNA) results to inform the decision for adjuvant chemotherapy in patients with locally advanced rectal cancer who have been treated with pre-operative chemo-radiation and surgery.
Scientific title
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Locally Advanced Rectal Cancer: A Multicentre Randomised Study (DYNAMIC-RECTAL)
Secondary ID [1] 293293 0
ctDNA-11
Universal Trial Number (UTN)
U1111-1204-7277
Trial acronym
DYNAMIC-Rectal
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally advanced rectal cancer treated with pre-operative long course chemo-radiation and surgery 305367 0
Condition category
Condition code
Cancer 304654 304654 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study involves blood collection for ctDNA analysis in patients with locally advanced rectal cancer who have undergone pre-operative long course chemo-radiation and surgery. Two ctDNA samples are collected initially in the outpatient setting; at weeks 4 and 7 post surgery. Patients are then randomised to either the standard of care (SOC) arm or the ctDNA-informed arm.
ctDNA-informed arm:
Patients who have either a positive ctDNA result OR a negative ctDNA result and have a tumour that is at high-risk of recurring (based on the standard pathology risk assessment of their tumour) will go on to have chemotherapy which will consist of 4 months of either 5FU or Capecitabine with or without Oxaliplatin. Up to a total of five ctDNA blood samples will be collected from each patient during (monthly) and at completion of chemotherapy.
SOC arm;
A decision regarding adjuvant chemotherapy will be based on the standard pathology risk assessment of their tumour. Chemotherapy will consist of 4 months of treatment with either 5FU or Capecitabine with or without Oxaliplatin. No further ctDNA samples will be collected in this group of patients.
All patients will be follow up in the outpatient setting every 3 months for the first 2 years then every 6 months for 3 years out to 5 years in total. In the follow up period, a blood test for CEA (carcinoembryonic antigen; a tumour marker) will be collected at each visit. A CT scan will be done every 6 months for the first 2 years then at 3 years and thereafter only if clinically indicated.

Intervention code [1] 299549 0
Early detection / Screening
Intervention code [2] 299550 0
Treatment: Drugs
Comparator / control treatment
Standard of care arm; The decision to have adjuvant chemotherapy or not will be based solely on the standard pathology risk assessment and not include ctDNA result.
Control group
Active

Outcomes
Primary outcome [1] 303875 0
To evaluate whether an adjuvant therapy strategy based on ctDNA results in addition to standard pathologic risk assessment may affect the number of patients treated with chemotherapy.
Timepoint [1] 303875 0
Patients from both Arms will be followed up every 3 months for the first 2 years and then every 6 months for the next 3 years.
Secondary outcome [1] 340328 0
To evaluate whether an adjuvant therapy strategy based on ctDNA results affects overall recurrence-free survival in patients with locally advanced rectal cancer. Recurrence is assessment by blood tests for CEA and CT scans.
Timepoint [1] 340328 0
Patients from both Arms will be followed up every 3 months for the first 2 years and then every 6 months for the next 3 years post surgery for recurrence.
Secondary outcome [2] 340329 0
To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect overall survival in patients with locally advanced rectal cancer
Timepoint [2] 340329 0
Patients from both Arms will be followed up every 3 months for the first 2 years and then every 6 months for the next 3 years post surgery for survival.
Secondary outcome [3] 340330 0
To correlate the change of serial ctDNA measurements during treatment with disease recurrence and overall survival.
Timepoint [3] 340330 0
Patients in the ct-DNA informed arm receiving chemotherapy will have monthly blood tests to measure their ctDNA levels for the duration of their chemotherapy treatment, and be followed up every 3 months for the first 2 years and then every 6 months for the next 3 years post surgery for recurrence and survival

Eligibility
Key inclusion criteria
1. Aged 18 years of age and over
2. Subjects with locally advanced rectal cancer treated with curative intent
3. Subjects treated with pre-operative long course chemo-radiation and surgery
4. CT scan of chest/abdomen/pelvis prior to commencing pre-operative chemo-radiation demonstrating no metastatic disease
5. A tumour sample (from the pre-treatment biopsy or surgery specimen is available for molecular testing within 35 days after surgery
6. Fit for adjuvant (post surgery) chemotherapy
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of another primary cancer within the last 3 years (with the exception of non-melanoma skin cancer and carcinoma in situ).
2. Patients with multiple primary colorectal cancers
3. Inadequate bone marrow, kidney and liver function, as determined by blood tests
4. Evidence of active infection
5. Clinically significant cardiovascular disease
6. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the study requirements

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Stratification by;
1. participating site and 2. by pathological stage of lymph node involvement (ypN0 vs ypN+) following pre-operative chemo-radiation and surgery.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This study is powered to show that a ctDNA-based approach to adjuvant therapy will lead to substantially fewer patients receiving adjuvant therapy.
To demonstrate non-inferiority with 80% power, alpha=0.05, and accounting for a 15% drop-out rate, 408 patients will need to be enrolled.

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 in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 9346 0
Western Hospital - Footscray - Footscray
Recruitment hospital [2] 9347 0
Western Private Hospital - Footscray
Recruitment hospital [3] 9348 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 9349 0
Melbourne Private Hospital - Parkville
Recruitment hospital [5] 9350 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 9351 0
The Northern Hospital - Epping
Recruitment hospital [7] 9352 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [8] 11683 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [9] 11684 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [10] 11685 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [11] 11686 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 18020 0
3011 - Footscray
Recruitment postcode(s) [2] 18021 0
3050 - Parkville
Recruitment postcode(s) [3] 18022 0
3052 - Parkville
Recruitment postcode(s) [4] 18023 0
3128 - Box Hill
Recruitment postcode(s) [5] 18024 0
3076 - Epping
Recruitment postcode(s) [6] 18025 0
3000 - Melbourne
Recruitment postcode(s) [7] 23729 0
3144 - Malvern
Recruitment postcode(s) [8] 23730 0
3550 - Bendigo
Recruitment postcode(s) [9] 23731 0
2290 - Gateshead
Recruitment postcode(s) [10] 23732 0
2298 - Waratah

Funding & Sponsors
Funding source category [1] 297916 0
Government body
Name [1] 297916 0
NHMRC
Address [1] 297916 0
Research Committee Secretariat
NHMRC
GPO Box 1421
Canberra ACT 2601
Country [1] 297916 0
Australia
Primary sponsor type
Other Collaborative groups
Name
AGITG
Address
GI Cancer Institute @ Lifehouse
Level 6, 119-143 Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 296976 0
None
Name [1] 296976 0
Address [1] 296976 0
Country [1] 296976 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298966 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 298966 0
Royal Melbourne Hospital
Level 2, South West
300 Grattan St, Parkville VIC 3050
Ethics committee country [1] 298966 0
Australia
Date submitted for ethics approval [1] 298966 0
26/07/2017
Approval date [1] 298966 0
01/09/2017
Ethics approval number [1] 298966 0
HREC/17/MH/235

Summary
Brief summary
The primary purpose of this study is to show that by using ctDNA results, in addition to assessing the risk of tumour recurrence by standard pathology assessments, the number of patients receiving adjuvant (post surgery) chemotherapy will be reduced.
Who is it for?
You may be eligible to join this study if you are aged 18 or over, and have received chemo-radiation followed by surgery for locally advanced rectal cancer.
Study details:
All patients enrolled in this study are randomly allocated (by chance) to one of two groups; Standard of care (SOC) group or the ctDNA-informed group. The decision to proceed with chemotherapy for those in the SOC group is based only on the standard risk assessment of the tumour (how likely your tumour is to come back or recur). Their ctDNA result will not be disclosed. Those who are randomised to the ctDNA-informed group will be treated with chemotherapy if they are ctDNA positive OR if they are ctDNA negative AND are considered to have a tumour at high risk of recurring based on the standard risk assessment. Only those in the ctDNA-informed group who have chemotherapy will have monthly ctDNA samples collected; up to four samples collected over 4 months then a final sample after chemotherapy has finished.
All participants will be followed up 3 monthly for 2 years, then 6 monthly for 3 years through their hospital for a total of five years for disease recurrence and survival.
It is hoped that the findings from this study will demonstrate that using ctDNA results to help make a decision as to who receives adjuvant chemotherapy will result in a reduction in the number of patients having chemotherapy and doing so, without compromising the rate of disease recurrence when compared to standard of care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78822 0
A/Prof Jeanne Tie
Address 78822 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052
Country 78822 0
Australia
Phone 78822 0
+61 3 9345 2893
Fax 78822 0
+61 3 9498 2010
Email 78822 0
jeanne.tie@petermac.org
Contact person for public queries
Name 78823 0
Ms Tina Cavicchiolo
Address 78823 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052
Country 78823 0
Australia
Phone 78823 0
+61 3 9345 2880
Fax 78823 0
+61 3 9345 2317
Email 78823 0
tina.cavicchiolo@mh.org.au
Contact person for scientific queries
Name 78824 0
A/Prof Jeanne Tie
Address 78824 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052
Country 78824 0
Australia
Phone 78824 0
+61 3 9345 2893
Fax 78824 0
+61 3 9498 2010
Email 78824 0
jeanne.tie@petermac.org

No data has been provided for results reporting
Summary results
Not applicable