ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12615000381583

Ethics application status

Approved

Date submitted

13/03/2015

Date registered

27/04/2015

Date last updated

11/06/2019

Date data sharing statement initially provided

11/06/2019

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]

Nil

Universal Trial Number (UTN)

Trial acronym

DYNAMIC

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Patients with the diagnosis of Stage II Colon cancer.

Patients with the diagnosis of stage II rectal cancer

Condition category

Condition code

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure

Study type

Interventional

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]

Early detection / Screening

Intervention code [2]

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

Active

Outcomes

Primary outcome [1]

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]

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]

To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect overall survival in patients with stage II colorectal cancer

Timepoint [1]

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]

To correlate the change of serial ctDNA measurements during treatment with disease recurrence.

Timepoint [2]

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.

Eligibility

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

Gender

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

Treatment

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

Parallel

Other design features

Phase

Not Applicable

Type of endpoint(s)

Efficacy

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

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/05/2015

Actual

10/08/2015

Date of last participant enrolment

Anticipated

1/01/2020

Actual

Date of last data collection

Anticipated

1/01/2025

Actual

Sample size

Target

450

Accrual to date

268

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [2]

Western Hospital - Footscray

Recruitment hospital [3]

The Alfred - Prahran

Recruitment hospital [4]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [5]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [6]

Bendigo Health Care Group - Bendigo Hospital - Bendigo

Recruitment hospital [7]

Border Medical Oncology - Albury

Recruitment hospital [8]

Cabrini Hospital - Malvern - Malvern

Recruitment hospital [9]

The Canberra Hospital - Garran

Recruitment hospital [10]

Box Hill Hospital - Box Hill

Recruitment hospital [11]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [12]

Flinders Medical Centre - Bedford Park

Recruitment hospital [13]

The Chris O’Brien Lifehouse - Camperdown

Recruitment hospital [14]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [15]

Nepean Hospital - Kingswood

Recruitment hospital [16]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [17]

Royal Hobart Hospital - Hobart

Recruitment hospital [18]

St John of God Hospital Warrnambool - Warrnambool

Recruitment hospital [19]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment hospital [20]

Calvary Mater Newcastle - Waratah

Recruitment hospital [21]

Newcastle Private Hospital - New Lambton Heights

Recruitment hospital [22]

The Northern Hospital - Epping

Recruitment postcode(s) [1]

3050 - Parkville

Recruitment postcode(s) [2]

5022 - Henley Beach

Recruitment postcode(s) [3]

3004 - Prahran

Recruitment postcode(s) [4]

3084 - Heidelberg

Recruitment postcode(s) [5]

3220 - Geelong

Recruitment postcode(s) [6]

3550 - Bendigo

Recruitment postcode(s) [7]

3690 - Wodonga

Recruitment postcode(s) [8]

3144 - Malvern

Recruitment postcode(s) [9]

2605 - Garran

Recruitment postcode(s) [10]

3128 - Box Hill

Recruitment postcode(s) [11]

6150 - Murdoch

Recruitment postcode(s) [12]

5042 - Bedford Park

Recruitment postcode(s) [13]

2050 - Camperdown

Recruitment postcode(s) [14]

3168 - Clayton

Recruitment postcode(s) [15]

2747 - Kingswood

Recruitment postcode(s) [16]

4029 - Herston

Recruitment postcode(s) [17]

7000 - Hobart

Recruitment postcode(s) [18]

3280 - Warrnambool

Recruitment postcode(s) [19]

3065 - Fitzroy

Recruitment postcode(s) [20]

2298 - Waratah

Recruitment postcode(s) [21]

2305 - New Lambton Heights

Recruitment postcode(s) [22]

3076 - Epping

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Walter and Eliza Hall Institute

Address

1G Royal Pde
Parkville
Vic 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

Post Office
Royal Melbourne Hospital
Parkville Victoria 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/11/2014

Approval date [1]

11/02/2015

Ethics approval number [1]

HREC/14/MH/355

Summary

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

Contacts

Principal investigator

Name

Dr Jeanne Tie

Address

Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050

Country

Australia

Phone

+61 3 9342 7695

Fax

jeanne.tie@mh.org.au

Contact person for public queries

Name

Mr Matthew Chapman

Address

Walter and Eliza Hall Institute
1G Royal Parade
Parkville VIC 3052

Country

Australia

Phone

+61 3 9345 2828

Fax

matthew.chapman@mh.org.au

Contact person for scientific queries

Name

Dr Jeanne Tie

Address

Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050

Country

Australia

Phone

+61 3 9342 7695

Fax

jeanne.tie@mh.org.au

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?

Study protocol
Statistical analysis plan
Informed consent form

How or where can supporting documents be obtained?

Type [1]

Informed consent form

Citation [1]

Link [1]

Email [1]

Other [1]

Attachment [1]

http://www.anzctr.org.au/Steps11and12/368173-(Uploaded-07-06-2019-12-11-27)-Study-related document.pdf

Summary results

No Results

Trial Review