
- DYNAMIC-Rectal
Trial Status
In Follow-up
Cancer Type
Rectal Cancer
Protocol Title
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Locally Advanced Rectal Cancer: A Multicentre Randomised Study (DYNAMIC-Rectal)
Purpose of the Study
Despite guidelines recommending the routine use of adjuvant chemotherapy in locally advanced rectal cancer (LARC), there is little evidence in the modern era to support the routine use of post-operative chemotherapy in patients who received pre-operative chemo-radiation therapy.
Our initial studies have demonstrated across multiple colorectal cancer cohorts, the potential utility of ctDNA as a marker of recurrence risk. The end goal for locally advanced rectal cancer patients is to integrate ctDNA analysis into routine clinical practice to guide clinical decision making, and most importantly to benefit patients.
This initial study is powered to show that a ctDNA-based approach to adjuvant therapy will lead to substantially less patients receiving adjuvant therapy, which we believe is the only practical study design with a clinically significant endpoint, within the patient numbers that could be recruited. Importantly, this study will also demonstrate the feasibility of performing such as biomarker-driven study in the rectal cancer.
Eligibility Criteria
Inclusion Criteria
- Aged 18 years of age and over
- Subjects with locally advanced rectal cancer treated with curative intent
- Subjects treated with pre-operative long course chemo-radiation and surgery
- CT scan of chest/abdomen/pelvis prior to commencing pre-operative chemo-radiation demonstrating no metastatic disease
- A tumour sample (from the pre-treatment biopsy or surgery specimen is available for molecular testing within 35 days after surgery)
- Fit for adjuvant (post surgery) chemotherapy
Exclusion criteria
- History of another primary cancer within the last 3 years (with the exception of non-melanoma skin cancer and carcinoma in situ).
- Patients with multiple primary colorectal cancers
- Inadequate bone marrow, kidney and liver function, as determined by blood tests
- Evidence of active infection
- Clinically significant cardiovascular disease
- Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the study requirements
Contact Email
Study Chairs
Associate Professor Jeanne Tie
Professor Peter Gibbs
DETAILED INFORMATION AVAILABLE
Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here
Funding
NHMRC project grant
Trial Status
In Follow-up
Cancer Type
Rectal Cancer
Protocol Title
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Locally Advanced Rectal Cancer: A Multicentre Randomised Study (DYNAMIC-Rectal)
AIM
Primary Objective:
- To demonstrate that an adjuvant therapy strategy incorporating ctDNA results in addition to standard pathologic risk assessment will reduce the number of patients receiving adjuvant chemotherapy
Secondary Objectives:
- To demonstrate that an adjuvant therapy strategy incorporating ctDNA results in addition to standard pathologic risk assessment will not compromise recurrence-free survival compared to standard of care
- To demonstrate that an adjuvant therapy strategy incorporating ctDNA results in addition to standard pathologic risk assessment will not compromise overall survival compared to standard of care
- To correlate any change in serial ctDNA measurements during adjuvant chemotherapy with disease recurrence and overall survival
BACKGROUND
Despite guidelines recommending the routine use of adjuvant chemotherapy in locally advanced rectal cancer (LARC), there is little evidence in the modern era to support the routine use of post-operative chemotherapy in patients who received pre-operative chemo-radiation therapy. In fact, the results of EORTC 22921 combined with the results of other smaller studies argue against the routine use of chemotherapy for patients with clinical stage II or III disease who are undergoing pre-operative chemo-radiotherapy. Although the use of adjuvant FOLFOX appears promising in node-positive disease (ypN+), this comes with a toxicity price and the impact on overall survival yet to be proven. Clearly, better predictors of those patients who actually require adjuvant chemotherapy are needed (e.g. ctDNA-positivity indicating presence of minimal residual disease).
Our initial studies have demonstrated across multiple colorectal cancer cohorts, the potential utility of ctDNA as a marker of recurrence risk. The end goal for LARC patients is to integrate ctDNA analysis into routine clinical practice to guide clinical decision making, and most importantly to benefit patients. This initial study is powered to show that a ctDNA-based approach to adjuvant therapy will lead to substantially less patients receiving adjuvant therapy, which we believe is the only practical study design with a clinically significant endpoint, within the patient numbers that could be recruited. Importantly, this study will also demonstrate the feasibility of performing such as biomarker-driven study in the rectal cancer population.
CLINICAL TRIAL DESIGN
Patients with locally advanced rectal cancer treated with standard chemo-radiation will be randomised 2:1 to be treated according to ctDNA results following surgery. In the ctDNA informed group (Arm B), patients with a positive post op ctDNA will receive 4 months of fluoropyrimidine or combination fluoropyrimidine plus oxaliplatin. Patients with a negative post-op ctDNA and pathological high risk disease will be treated at the clinician’s discretion whilst patients with intermediate or low risk disease will not be treated with adjuvant chemotherapy. In the standard of care group (Arm A), patients will receive 4 months of adjuvant chemotherapy or no adjuvant therapy at the discretion of the treating clinician.
Patients Recruited
Click here to access the table and view recruitment data on all AGITG open trials:
Contact Email
DYNAMIC-RECTAL@mh.org.auPrincipal Investigator
A/Professor Jeanne Tie
Detailed Information Available on
MORE DETAILED INFORMATION: Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here
FUNDING
NHMRC project grant