Tracking Mutations in Cell Free Tumour DNA to Predict Relapse in Early Colorectal Cancer

TRACC Part B Inclusion Criteria:

• New diagnosis of histologically confirmed CRC scheduled to undergo surgery withcurative intent, with no radiological evidence of metastatic disease.

• Patients with high grade dysplasia whose imaging is suggestive of colorectalcarcinoma (CRC) will be included but will be excluded post-surgery if carcinomadiagnosis is not confirmed

• Age≥18

• Ability to give informed consent

• Able to adhere to follow up schedule

TRACC Part B Exclusion Criteria:

• Scheduled to have neoadjuvant chemotherapy, (neoadjuvant chemoradiotherapy forpatients with rectal cancer is permitted)

• Current or previous other malignancy within 5 years of study entry, except curedbasal or squamous cell skin cancer, superficial bladder cancer, prostateintraepithelial neoplasm, carcinoma in situ of the cervix or other non-invasivemalignancy

TRACC Part C

Inclusion Criteria:

1. Subject ≥ 18 years of age

2. Subjects with histologically proven high risk stage II or stage III colon or rectalcancer treated with curative intent with surgery alone (any T, N1 or N2) with noevidence of metastatic disease. High risk stage II is defined as having one or moreof the following: T4 disease, obstruction and/or perforation of the primary tumourduring the pre-operative period, inadequate nodal harvest as indicated by <12 nodesexamined, poorly differentiated grade on histology, perineural invasion, peritonealinvolvement or extramural venous/lymphatic invasion. Subjects must be due to receiveadjuvant chemotherapy after surgery or Subjects with histologically proven locallyadvanced stage III rectal cancer treated with neoadjuvant chemoradiotherapy (any T,N1 or N2, M0) with no evidence of metastatic disease are eligible. Subjects must bedue to receive adjuvant chemotherapy after surgery

3. Fully surgically resected tumour with clear resection margins (i.e., >1 mm).

4. Adequate organ function

• Absolute neutrophil function ≥1.0 x 109/ L

• Platelet Count ≥ 75 x 109 / L

• Haemoglobin ≥80g/L (blood transfusion before randomisation is allowed)

• Adequate renal function (GFR ≥ 50ml/min if single agent capecitabine or CAPOXbeing administered) as calculated by Cockcroft and Gault equation

• Aspartate aminotransferase/ Alanine aminotransferase levels ≤ 2.5 upper limitof normal

5. Absence of major post-operative complications or other clinical conditions that, inthe opinion of the investigator, would contraindicate adjuvant chemotherapy

6. Patients should be assessed by Oncology team for suitability and assessment foradjuvant chemotherapy, be able to have post-operative ctDNA sample collected and berandomised by week 8 ± 2 weeks after surgery.

7. ECOG performance status 0- 2

8. Able to give informed consent

TRACC Part C Exclusion criteria

1. History of concurrent and previous malignancy within the last 5 years, with theexception of non- melanomatous skin cancer and carcinoma in situ 2. Any majorpost-operative complications or other clinical conditions that in the opinion of theinvestigator would contra-indicate adjuvant chemotherapy 3. Any subject not due toreceive adjuvant chemotherapy will not be eligible for Part C of the study 4.Hypersensitivity or contraindication to the drug(s) associated with the plannedchoice of systemic chemotherapy (CAPOX or single agent capecitabine) as stated inthe SmPC for each of the drugs 5. Subjects due to receive 5-Flurouracil (5-FU) basedadjuvant chemotherapy (either single agent 5-FU or in combination with oxaliplatin)will not be eligible for Part C of the study