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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
Circulating tumour DNA (ctDNA) analysis informing adjuvant chemotherapy in Stage II Colon Cancer
Scientific title
A study to evaluate the use of circulating tumour DNA to guide adjuvant chemotherapy on recurrence-free survival in patients with stage II Colon or rectal cancer.
Secondary ID [1] 286348 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with the diagnosis of Stage II Colon cancer. 294472 0
Patients with the diagnosis of stage II rectal cancer 294791 0
Condition category
Condition code
Cancer 294775 294775 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Study type
Description of intervention(s) / exposure
This is a randomized, multi-centre, biomarker driven adjuvant treatment study involving the collection of blood samples from subjects with curatively resected Stage II colon and rectal cancer. 450 consecutive eligible subjects will be enrolled at participating centres after informed consent is obtained. Patients will be enrolled within 28 days post surgery. Subjects will be randomized 2:1 to be treated according to the ctDNA results (Arm A, n=300), or per standard clinical criteria at the discretion of the treating clinician (Arm B, n=150). Resected tumour samples will be made available for mutation analyses. Patients must not have undergone pre-operative chemotherapy or radiotherapy.
All patients enrolled will have a blood sample taken at enrollment (week 4) and 3 weeks later (week 7) for initial ctDNA testing.
Patients randomized to Arm A and who have positive ctDNA result will receive adjuvant chemotherapy, patients with negative ctDNA result will not receive chemotherapy.
Patients randomized to Arm B will be treated at their clinicians discretion. The clinician will initially be blinded to their ctDNA result but results will be provided at or after 6 months post-op following a written request from the site investigator.
Patients treated with chemotherapy will receive single agent 5FU-based regimen (including capecitabine) or fluoropyrimidine plus oxaliplatin .
Acceptable fluoropyrimidine based chemotherapy regimens include 3-6 months weeks of:
1. 2 weekly De Gramont (modified)
a. Leucovorin 50mg IV
b. Fluorouracil 400mg/m2 IV
c. Fluorouracil 2400mg/m2 CIV pump over 46 hours
2. Weekly modified QUASAR
a. Leucovorin 50mg IV
b. Fluorouracil 375-450mg/m2 IV (dose as per institutional standard of care)
3. Weekly modified Roswell Park (weekly for 6 weeks followed by 2 week break)
a. Leucovorin 50mg IV
b. Fluorouracil 500mg/m2 IV
4. Capecitabine PO days 1 to 14, Q21 days (dose as per institutional standard of care)

Acceptable Oxaliplatin-based chemotherapy regimens include 3-6 months of:
1. 2 weekly FOLFOX6 (modified)
a. Oxaliplatin 85mg/m2 IV
b. Leucovorin 50mg IV
c. Fluorouracil 400mg/m2 IV
d. Fluorouracil 2400mg/m2 CIV pump over 46 hours
2. 3 weekly XELOX/CAPOX
a. Oxaliplatin 130mg/m2
b. Capecitabine 1000mg/m2 twice a day PO days 1 to 14, Q21 days
Intervention code [1] 291411 0
Early detection / Screening
Intervention code [2] 291651 0
Treatment: Other
Comparator / control treatment
Patients enrolled in Arm B will be blinded to the ctDNA result and will be treated as per standard clinical criteria at the discretion of the treating clinician.
Control group

Primary outcome [1] 294538 0
To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect the number of patients treated with chemotherapy and recurrence-free survival.
Recurrence will be assessed through protocol specified follow up regimen, including 3 monthly CEA tests and 6 monthly CT scans.
Timepoint [1] 294538 0
Patients from all 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 [1] 313576 0
To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect overall survival in patients with stage II colorectal cancer
Timepoint [1] 313576 0
Patients from all 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 [2] 313696 0
To correlate the change of serial ctDNA measurements during treatment with disease recurrence.
Timepoint [2] 313696 0
Patients in Arm A receiving chemotherapy will have monthly blood tests to measure their ctDNA levels, 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.

Key inclusion criteria
1. Subjects with curatively resected stage II (T3-4, N0M0) colon or rectal cancer.
2. Patients with rectal cancer will be eligible unless they have had pre-operative combined chemotherapy or radiotherapy, or are scheduled for post-operative combined chemotherapy and radiotherapy. All rectal cancer patients included in the trial must have had TME type surgery with negative (R0) resection margins.
3. A representative paraffin embedded tumour sample is avaiable for molecular testing.
4. Fit for adjuvant chemotherapy.
5. ECOG performance status 0-2.
6. Patients that are accessible for follow up.
7. CT C/A/P within 8 weeks demonstrating no metastatic disease.
Minimum age
18 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
1. History of another primary cancer within the last 3 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix.
2. Patients with multiple primary colorectal cancers
3. Patients treated with neoadjuvant chemo-radiation.
4. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol.

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the Sponsor Site who holds the randomized allocation table.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomisation table created by statistical software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?

Intervention assignment
Other design features
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
It is anticipated that 10% of patients will have detectable ctDNA. The study will need to enrol 450 patients to recruit 30 patients with detectable post op ctDNA into Arm A. This will achieve an 80% power at a=0.1 to demonstrate non-inferiority in Arm A.

Recruitment status
Active, not recruiting
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 6665 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 6666 0
Western Hospital - Footscray
Recruitment hospital [3] 6667 0
The Alfred - Prahran
Recruitment hospital [4] 6668 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 6669 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [6] 6670 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [7] 6671 0
Border Medical Oncology - Albury
Recruitment hospital [8] 6672 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [9] 6673 0
The Canberra Hospital - Garran
Recruitment hospital [10] 6674 0
Box Hill Hospital - Box Hill
Recruitment hospital [11] 6675 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [12] 6676 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [13] 6677 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [14] 6678 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [15] 6679 0
Nepean Hospital - Kingswood
Recruitment hospital [16] 6680 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [17] 6681 0
Royal Hobart Hospital - Hobart
Recruitment hospital [18] 6682 0
St John of God Hospital Warrnambool - Warrnambool
Recruitment hospital [19] 6683 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [20] 8812 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [21] 8813 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [22] 11457 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 14291 0
3050 - Parkville
Recruitment postcode(s) [2] 14292 0
5022 - Henley Beach
Recruitment postcode(s) [3] 14293 0
3004 - Prahran
Recruitment postcode(s) [4] 14294 0
3084 - Heidelberg
Recruitment postcode(s) [5] 14295 0
3220 - Geelong
Recruitment postcode(s) [6] 14296 0
3550 - Bendigo
Recruitment postcode(s) [7] 14297 0
3690 - Wodonga
Recruitment postcode(s) [8] 14298 0
3144 - Malvern
Recruitment postcode(s) [9] 14299 0
2605 - Garran
Recruitment postcode(s) [10] 14300 0
3128 - Box Hill
Recruitment postcode(s) [11] 14301 0
6150 - Murdoch
Recruitment postcode(s) [12] 14302 0
5042 - Bedford Park
Recruitment postcode(s) [13] 14303 0
2050 - Camperdown
Recruitment postcode(s) [14] 14304 0
3168 - Clayton
Recruitment postcode(s) [15] 14305 0
2747 - Kingswood
Recruitment postcode(s) [16] 14306 0
4029 - Herston
Recruitment postcode(s) [17] 14307 0
7000 - Hobart
Recruitment postcode(s) [18] 14308 0
3280 - Warrnambool
Recruitment postcode(s) [19] 14309 0
3065 - Fitzroy
Recruitment postcode(s) [20] 16935 0
2298 - Waratah
Recruitment postcode(s) [21] 16936 0
2305 - New Lambton Heights
Recruitment postcode(s) [22] 23476 0
3076 - Epping

Funding & Sponsors
Funding source category [1] 290922 0
Government body
Name [1] 290922 0
Address [1] 290922 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 290922 0
Primary sponsor type
Other Collaborative groups
Walter and Eliza Hall Institute
1G Royal Pde
Vic 3052
Secondary sponsor category [1] 289608 0
Name [1] 289608 0
Address [1] 289608 0
Country [1] 289608 0

Ethics approval
Ethics application status
Ethics committee name [1] 292527 0
Melbourne Health HREC
Ethics committee address [1] 292527 0
Post Office
Royal Melbourne Hospital
Parkville Victoria 3050
Ethics committee country [1] 292527 0
Date submitted for ethics approval [1] 292527 0
Approval date [1] 292527 0
Ethics approval number [1] 292527 0

Brief summary
This study will determine the effect of the use of circulating tumour DNA (ctDNA) to guide adjuvant chemotherapy on recurrence-free survival in stage II colon or rectal cancer patients

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with Stage II colon or rectal cancer and have had your cancer curatively resected.

Study details
Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will have blood samples taken and analysed for circulating tumour DNA (ctDNA) and be treated according to the ctDNA results. Those with positive ctDNA results will receive standard 5FU-based adjuvant chemotherapy (either single agent or combined with oxaliplatin), while those with negative ctDNA will not receive adjuvant chemotherapy.
Participants in the other group will have a blood sample taken, but the ctDNA result will not be disclosed. Patients in this group will be treated according to standard clinical criteria at the discretion of the treating physician.
Participants who had positive ctDNA results and are being treated with adjuvant chemotherapy will have monthly blood samples taken during treatment to track ctDNA levels. 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.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 55750 0
A/Prof Jeanne Tie
Address 55750 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne VIC 3000
Country 55750 0
Phone 55750 0
+61 3 9345 2707
Fax 55750 0
Email 55750 0
Contact person for public queries
Name 55751 0
Mr Matthew Chapman
Address 55751 0
Walter and Eliza Hall Institute
1G Royal Parade
Parkville VIC 3052
Country 55751 0
Phone 55751 0
+61 3 9345 2828
Fax 55751 0
Email 55751 0
Contact person for scientific queries
Name 55752 0
A/Prof Jeanne Tie
Address 55752 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne VIC 3000
Country 55752 0
Phone 55752 0
+61 3 9345 2707
Fax 55752 0
Email 55752 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
IPD may be collected at a site level. However, IPD will not be made available to the Sponsor. The data that is collected by the Sponsor will not be re-identifiable at the Sponser level. There are safeguards in place to minimise the risk of a privacy breach. They include analysing the data on an aggregated level and access to the data in a controlled environment with only authorised study personnel. Finally, enabling the availability of IPDs will not help meet the primary and secondary objectives of the study which are dependent on the results from the study population rather than on an individual basis.
What supporting documents are/will be available?
Informed consent form
How or where can supporting documents be obtained?
Type [1] 2291 0
Informed consent form
Citation [1] 2291 0
Link [1] 2291 0
Email [1] 2291 0
Other [1] 2291 0
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary