TRACC C

Eligibility criteria to be used prior to registration (for all patients, Part A and B): 

Inclusion Criteria: 

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

• Patients with lesions with high degree of suspicion on histology but not confirmed to be an adenocarcainoma and whose imaging is strongly suggestive of colorectal carcinoma (CRC) will be included. This patients will be excluded post-surgery if carcinoma diagnosis is not confirmed 

• Age≥18 • Ability to give informed consent 

• Able to adhere to follow up schedule Additional eligibility criteria for rectal cancer patients following completion of pre-operative radiotherapy or chemoradiotherapy All patients proceeding to surgery Eligibility criteria at the first post-operative visit: Inclusion Criteria: 

• Stage I, II or III CRC based on the post-operative histopathology report 

• Availability of FFPE tumour tissue from surgery, for processing and analysis at the CMP For patients in the ctDNA guided interventional arm of the study only (Part C) Inclusion Criteria: 

1. Subject ≥ 18 years of age 

2. Subjects with histologically proven high risk stage II or stage III colon or rectal cancer treated with curative intent with surgery alone (any T, N1 or N2) with no evidence of metastatic disease. Subjects must be due to receive adjuvant chemotherapy following surgery. Subjects with histologically proven stage III rectal cancer are eligible, including patients treated with neoadjuvant chemoradiotherapy (any T, N1 or N2, M0) with no evidence of metastatic disease. Subjects must be due to receive adjuvant chemotherapy following surgery. 

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

4. Patients must have detectable levels of ctDNA (i.e., ctDNA positive) in blood samples at baseline; this is collected pre-operatively if being treated with surgery alone, or before chemoradiotherapy in patients with locally advanced rectal cancer being treated with neoadjuvant chemoradiotherapy before surgery 

5. 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 as calculated by Cockcroft and Gault equation (GFR ≥ 30ml/min if FOLFOX chemotherapy chosen and GFR ≥ 50ml/min if single agent capecitabine or CAPOX chosen) - Aspartate aminotransferase/ Alanine aminotransferase levels ≤ 2.5 upper limit of normal 

6. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would not contraindicate adjuvant chemotherapy 

7. Patients should be assessed by Oncology team for suitability and assessment for adjuvant chemotherapy, be able to have post-operative ctDNA sample collected and be randomised by week 4-8 after surgery. 

8. ECOG performance status 0- 2 

9. Able to give informed consent 

Eligibility criteria to be used prior to registration (for all patients, Part A and B): 

Exclusion Criteria: 

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

• Current or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix or other non-invasive malignancy. Additional eligibility criteria for rectal cancer patients following completion of pre-operative radiotherapy or chemoradiotherapy Patients scheduled to have further pre-operative treatment with chemotherapy 

• Patients that are no longer proceeding with surgery i.e. those in whom surgery is considered too high risk 

• Patients that are no longer proceeding with surgery as they are proceeding with a deferral of surgery approach Eligibility criteria at the first post-operative visit: Patients with no confirmed tissue diagnosis or high grade dysplasia included in the study based on imaging diagnosis but subsequent histopathology of surgical specimen confirms no carcinoma will be excluded 

• Scheduled to receive post-operative radiotherapy For patients in the ctDNA guided interventional arm of the study only (Part C) 

Exclusion Criteria: 

1. History of concurrent and previous malignancy within the last 3 years, with the exception of non- melanomatous skin cancer and carcinoma in situ 

2. Any major post-operative complications or other clinical conditions that in the opinion of the investigator would contra-indicate adjuvant chemotherapy 

3. Any subject not due to receive adjuvant chemotherapy will not be eligible for Part C of the study 

4. Hypersensitivity or contraindication to the drug(s) associated with the planned choice of systemic chemotherapy (CAPOX, FOLFOX or single agent 5-FU or capecitabine) as stated in the SPC for each of the drugs 

Lead Research Nurse: Rashmi Madan (x2136) Rashmi.Madan@LTHTR.nhs.uk

Clinical Trials Administrator : Yecora Lecanda-Swarbrick (x3766)