DYNAMIC-Rectal

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:

Open Trial Recruitment Table

Contact Email

Principal 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