ANZCTR - Registration

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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

22/12/2021

Date data sharing statement initially provided

19/08/2019

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]

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

Condition category

Condition code

Cancer

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]

Early detection / Screening

Intervention code [2]

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]

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]

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]

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

Timepoint [1]

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

Secondary outcome [2]

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 [2]

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 [3]

To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect overall survival in patients with locally advanced rectal cancer

Timepoint [3]

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.

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

Sex

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-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

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Participant recruitment difficulties
Other reasons/comments

Other reasons

Accrual had slowed due to COVID-19 and adoption of TNT approach in this population therefore target number would not have been reached within the planned recruitment period.

Date of first participant enrolment

Anticipated

4/12/2017

Actual

27/07/2018

Date of last participant enrolment

Anticipated

31/12/2022

Actual

30/09/2021

Date of last data collection

Anticipated

30/09/2023

Actual

Sample size

Target

408

Accrual to date

Final

250

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,WA,VIC

Recruitment hospital [1]

Wollongong Hospital - Wollongong

Recruitment hospital [2]

Southwest Health Care - Warrnambool - Warrnambool

Recruitment hospital [3]

Melbourne Private Hospital - Parkville

Recruitment hospital [4]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [5]

The Northern Hospital - Epping

Recruitment hospital [6]

Western Hospital - Footscray - Footscray

Recruitment hospital [7]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [8]

Box Hill Hospital - Box Hill

Recruitment hospital [9]

The Tweed Hospital - Tweed Heads

Recruitment hospital [10]

Bendigo Health Care Group - Bendigo Hospital - Bendigo

Recruitment hospital [11]

Western Private Hospital - Footscray

Recruitment hospital [12]

Gosford Hospital - Gosford

Recruitment hospital [13]

Port Macquarie Base Hospital - Port Macquarie

Recruitment hospital [14]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [15]

Cabrini Hospital - Malvern - Malvern

Recruitment hospital [16]

The Alfred - Melbourne

Recruitment hospital [17]

St Vincent's Private Hospital (Werribee) - Werribee

Recruitment hospital [18]

Westmead Hospital - Westmead

Recruitment hospital [19]

Calvary Mater Newcastle - Waratah

Recruitment hospital [20]

Epworth Eastern Hospital - Box Hill

Recruitment hospital [21]

Cairns Base Hospital - Cairns

Recruitment hospital [22]

The Canberra Hospital - Garran

Recruitment hospital [23]

Epworth Richmond - Richmond

Recruitment hospital [24]

Peninsula Private Hospital - Frankston - Frankston

Recruitment hospital [25]

Latrobe Regional Hospital - Traralgon

Recruitment hospital [26]

Nepean Hospital - Kingswood

Recruitment hospital [27]

Lake Macquarie Private Hospital - Gateshead

Recruitment hospital [28]

Peninsula Oncology Centre - Frankston

Recruitment hospital [29]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [30]

Toowoomba Hospital - Toowoomba

Recruitment hospital [31]

Sunshine Coast University Hospital - Birtinya

Recruitment hospital [32]

Goulburn Valley Health - Shepparton campus - Shepparton

Recruitment hospital [33]

Tamworth Rural Referral Hospital - Tamworth

Recruitment hospital [34]

St Vincent's Hospital (Darlinghurst) - Darlinghurst

Recruitment hospital [35]

Royal Darwin Hospital - Tiwi

Recruitment hospital [36]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment hospital [37]

St Vincent's Private Hospital - Fitzroy

Recruitment postcode(s) [1]

2500 - Wollongong

Recruitment postcode(s) [2]

3630 - Shepparton

Recruitment postcode(s) [3]

3000 - Melbourne

Recruitment postcode(s) [4]

3052 - Parkville

Recruitment postcode(s) [5]

3076 - Epping

Recruitment postcode(s) [6]

2340 - Tamworth

Recruitment postcode(s) [7]

3128 - Box Hill

Recruitment postcode(s) [8]

2747 - Kingswood

Recruitment postcode(s) [9]

3011 - Footscray

Recruitment postcode(s) [10]

3199 - Frankston

Recruitment postcode(s) [11]

3050 - Parkville

Recruitment postcode(s) [12]

2298 - Waratah

Recruitment postcode(s) [13]

3065 - Fitzroy

Recruitment postcode(s) [14]

3128 - Box Hill

Recruitment postcode(s) [15]

2605 - Garran

Recruitment postcode(s) [16]

2444 - Port Macquarie

Recruitment postcode(s) [17]

2010 - Darlinghurst

Recruitment postcode(s) [18]

3121 - Richmond

Recruitment postcode(s) [19]

2290 - Gateshead

Recruitment postcode(s) [20]

3144 - Malvern

Recruitment postcode(s) [21]

3168 - Clayton

Recruitment postcode(s) [22]

3550 - Bendigo

Recruitment postcode(s) [23]

4870 - Cairns

Recruitment postcode(s) [24]

3844 - Traralgon

Recruitment postcode(s) [25]

3030 - Werribee

Recruitment postcode(s) [26]

4350 - Toowoomba

Recruitment postcode(s) [27]

3280 - Warrnambool

Recruitment postcode(s) [28]

2250 - Gosford

Recruitment postcode(s) [29]

0810 - Tiwi

Recruitment postcode(s) [30]

4575 - Birtinya

Recruitment postcode(s) [31]

6150 - Murdoch

Recruitment postcode(s) [32]

3065 - Fitzroy

Recruitment postcode(s) [33]

2145 - Westmead

Recruitment postcode(s) [34]

2485 - Tweed Heads

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Christchurch

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

Research Committee Secretariat
NHMRC
GPO Box 1421
Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Royal Melbourne Hospital
Level 2, South West
300 Grattan St, Parkville VIC 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/07/2017

Approval date [1]

01/09/2017

Ethics approval number [1]

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

A/Prof Jeanne Tie

Address

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052

Country

Australia

Phone

+61 3 9345 2893

Fax

+61 3 9498 2010

jeanne.tie@petermac.org

Contact person for public queries

Name

Tina Cavicchiolo

Address

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052

Country

Australia

Phone

+61 499250152

Fax

+61, 03, 94982010

tina.cavicchiolo@mh.org.au

Contact person for scientific queries

Name

Jeanne Tie

Address

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville Victoria, 3052

Country

Australia

Phone

+61 3 9345 2893

Fax

+61 3 9498 2010

jeanne.tie@petermac.org

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

IPD will not be available

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Impact of circulating tumor DNA early detection and serial monitoring in the management of stage I to III colorectal cancer.	2019	https://dx.doi.org/10.21037/atm.2019.10.30
Dimensions AI	Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer	2019	https://doi.org/10.1001/jamaoncol.2019.3616
Dimensions AI	Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality	2019	https://doi.org/10.1200/po.18.00397
Embase	Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.	2020	https://dx.doi.org/10.1016/j.ctrv.2019.101948
Dimensions AI	Circulating Tumour DNA to Guide Treatment of Gastrointestinal Malignancies	2020	https://doi.org/10.1159/000509657
Dimensions AI	Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies	2020	https://doi.org/10.1002/ijc.33312
Dimensions AI	Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer	2021	https://doi.org/10.3390/cancers13184547
Embase	Total neoadjuvant therapy: Fact, fantasy, or fallacy?.	2022	https://dx.doi.org/10.1016/j.suronc.2022.101738
Embase	Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices.	2022	https://dx.doi.org/10.1200/JCO.21.02615
Dimensions AI	Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer	2022	https://doi.org/10.1001/jamanetworkopen.2022.1093

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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Documents added manually

Documents added automatically