Tracking Mutations in Cell Free Tumour DNA to Predict Relapse in Early Colorectal Cancer
- Conditions
- Colorectal Cancer
- Registration Number
- NCT04050345
- Lead Sponsor
- Royal Marsden NHS Foundation Trust
- Brief Summary
TRACC Part B This is a multi-centre, prospective, translational research study involving the collection and analysis of tumour tissue, serial blood samples and clinical data in patients with newly diagnosed stage I, II and III CRC.
TRACC Part C is a : (multi-centre, prospective, randomised study, of ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy study after curative surgery in patients with high risk stage II or stage III CRC. )It aims to demonstrate that a de-escalation strategy of ctDNA guided adjuvant chemotherapy is non- inferior to standard of care treatment as measured by 3 year disease free survival (DFS) in patients with high risk stage II or stage III colorectal cancer CRC with no evidence of minimal residual disease (MRD) (ctDNA negative)
- Detailed Description
TRACC Part B: Despite potentially curative surgery +/- adjuvant chemotherapy, a proportional of patients with early stage CRC will experience disease relapse. Current tools for surveillance, e.g., blood sampling for tumour markers (CEA) are neither sensitive nor specific. We hypothesise that detection of mutations in circulating free DNA (cfDNA) in plasma can predict relapse in patients with early stage CRC.
Circulating cell free tumour DNA (ctDNA) maintains the same mutations that are present in tumour. In colorectal cancer CRC, primary tumours and\& metastases exhibit high genomic concordance. Therefore the TRACC study TRACC Part B is investigating whether serial blood samples taken from in patients with stage II and III fully resected early stage CRC colorectal cancer that have undergone potentially curative surgery, blood samples to can be used to detect and\& quantify ctDNA may in order to identify minimal residual disease MRD and predict relapse earlier than existing methods. CtDNA may ultimately help identify a subset of patients that are or are unlikely to benefit from adjuvant chemotherapy and could therefore safely spare some patients from receiving unnecessary chemotherapy \& its associated side-effects.
TRACC Part C: We hypothesis that ctDNA guided adjuvant chemotherapy administration will enable biomarker driven selection of patients who would and would not benefit from adjuvant chemotherapy and thereby reduce the proportion of patient receiving unnecessary adjuvant chemotherapy, reducing the potential side effects associated with it, but without compromising disease free survival (DFS). : This part of the study will use tThe blood test ctDNA result from a post-operative blood sample willto guide adjuvant chemotherapy treatment decisions. The study aims to demonstrate that athe de -escalation strategy of ctDNA guided adjuvant chemotherapy is non-inferior to standard of care treatment as measured by 3 year DFS in patients with high risk stage II and stage III CRC, in those who have no evidence of MRD (ctDNA negative). after surgery for patients with colorectal cancer who are following the standard of care pathway. Patients are randomised at the post- operative time point to: Arm A (standard of care adjuvant chemotherapy), or Arm B (ctDNA guided adjuvant chemotherapy) arm. For the ct DNA guided arm, patients who are ctDNA negative at this time point will have their chemotherapy de-escalated.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1000
- New diagnosis of histologically confirmed CRC scheduled to undergo surgery with curative intent, with no radiological evidence of metastatic disease.
- Patients with high grade dysplasia whose imaging is suggestive of colorectal carcinoma (CRC) will be included but 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
TRACC Part B
- 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
TRACC Part C
Inclusion Criteria:
-
Subject ≥ 18 years of age
-
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. High risk stage II is defined as having one or more of the following: T4 disease, obstruction and/or perforation of the primary tumour during the pre-operative period, inadequate nodal harvest as indicated by <12 nodes examined, poorly differentiated grade on histology, perineural invasion, peritoneal involvement or extramural venous/lymphatic invasion. Subjects must be due to receive adjuvant chemotherapy after surgery or Subjects with histologically proven locally advanced stage III rectal cancer treated with neoadjuvant chemoradiotherapy (any T, N1 or N2, M0) with no evidence of metastatic disease are eligible. Subjects must be due to receive adjuvant chemotherapy after surgery
-
Fully surgically resected tumour with clear resection margins (i.e., >1 mm).
-
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 CAPOX being administered) as calculated by Cockcroft and Gault equation
- Aspartate aminotransferase/ Alanine aminotransferase levels ≤ 2.5 upper limit of normal
-
Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy
-
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 8 ± 2 weeks after surgery.
-
ECOG performance status 0- 2
-
Able to give informed consent
TRACC Part C Exclusion criteria
- History of concurrent and previous malignancy within the last 5 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 or single agent capecitabine) as stated in the SmPC for each of the drugs 5. Subjects due to receive 5-Flurouracil (5-FU) based adjuvant chemotherapy (either single agent 5-FU or in combination with oxaliplatin) will not be eligible for Part C of the study
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method TRACC Part B (Translational sub study) 6 years • To assess whether detection of ctDNA predicts for relapse in patients with stage II and III colorectal cancer (CRC) that have undergone surgery with curative intent
TRACC Part C (Randomised ctDNA guided adjuvant chemotherapy versus SoC study): 4 years • To demonstrate de-escalation strategy of ctDNA guided adjuvant chemotherapy is non- inferior to standard of care treatment as measured by 3 year disease free survival in patients with high risk stage II or stage III colorectal cancer with no evidence of minimal residual disease (ctDNA negative)
- Secondary Outcome Measures
Name Time Method Relationship between ctDNA detection before, during and after treatment 8 years To calculate the association between detectable ctDNA with disease free survival and overall survival at four time points during treatment.
Trial Locations
- Locations (71)
Musgrove Park Hospital
🇬🇧Taunton, Somerset, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
North Cumbria University Hospitals
🇬🇧Carlisle, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Wycombe Hospital
🇬🇧High Wycombe, United Kingdom
Forth Valley Royal Hospital
🇬🇧Larbert, United Kingdom
Queen Alexandra Hospital
🇬🇧Portsmouth, Hampshire, United Kingdom
Weston General Hospital
🇬🇧Weston-super-Mare, Somerset, United Kingdom
Royal Blackburn Teaching Hospital
🇬🇧Blackburn, United Kingdom
Pilgrim Hospital
🇬🇧Boston, United Kingdom
Calderdale and Huddersfield NHS Foundation Trust
🇬🇧Huddersfield, United Kingdom
Kettering General Hospital
🇬🇧Kettering, United Kingdom
Royal Shrewsbury Hospital
🇬🇧Shrewsbury, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Stoke Mandeville Hospital
🇬🇧Aylesbury, United Kingdom
Croydon University Hospital
🇬🇧Thornton Heath, Croydon, United Kingdom
University Hospital of South Manchester & Manchester Royal Infirmary
🇬🇧Wythenshawe, Manchester, United Kingdom
Epsom and St Helier's Hospitals NHS Trust
🇬🇧Carshalton, Surrey, United Kingdom
Guy's & St Thomas Hospital
🇬🇧London, UK, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, Whiltshire, United Kingdom
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, West Yorkshire, United Kingdom
Basingstoke and North Hampshire Hospitals
🇬🇧Basingstoke, United Kingdom
Bedford Hospital
🇬🇧Bedford, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Withybush General Hospital
🇬🇧Haverfordwest, United Kingdom
George Eliot Hospital
🇬🇧Nuneaton, United Kingdom
Barking Havering and Redbridge NHS Foundation Trust (Queen's Hospital
🇬🇧Romford, United Kingdom
King's Mill Hospital
🇬🇧Sutton In Ashfield, United Kingdom
The Royal Marsden NHS Foundation Trust - London
🇬🇧London, United Kingdom
Dorset County Hospital NHS Foundation Trust
🇬🇧Dorchester, Dorset, United Kingdom
Poole Hospital
🇬🇧Poole, Dorset, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Christie NHS Foundation Trust
🇬🇧Manchester, Greater Manchester, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Bronglais Hospital
🇬🇧Aberystwyth, United Kingdom
Basildon and Thurrock University Hospitals
🇬🇧Basildon, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
University Hospitals Coventry & Warwickshire
🇬🇧Coventry, United Kingdom
Airedale General Hospital
🇬🇧Keighley, United Kingdom
Kingston Hospital Foundation Trust
🇬🇧Kingston Upon Thames, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
Prince Philip Hospital
🇬🇧Llanelli, United Kingdom
Maidstone & Tunbridge Wells NHS Trust
🇬🇧Maidstone, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
Burnley General Teaching Hospital
🇬🇧Burnley, United Kingdom
West Suffolk Hospital
🇬🇧Bury, United Kingdom
Glangwili Hospital
🇬🇧Carmarthen, United Kingdom
Leighton Hospital
🇬🇧Crewe, United Kingdom
University Hospital Crosshouse
🇬🇧Crosshouse, United Kingdom
Medway NHS Foundation Trust
🇬🇧Gillingham, United Kingdom
Royal Preston Hospital, Lancashire Teaching Hospitals
🇬🇧Preston, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Wrightington, Wigan and Leigh NHS Foundation Trust
🇬🇧Wigan, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Chase Farm Hospital
🇬🇧Middlesex, United Kingdom
Northampton General Hospital NHS Trust
🇬🇧Northampton, United Kingdom
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
University Hospital Southampton
🇬🇧Southampton, United Kingdom
Stockport NHS Foundation Trust
🇬🇧Stockport, United Kingdom
North Middlesex University Hospital NHS Trust
🇬🇧London, United Kingdom
St George's NHS Foundation Trust
🇬🇧London, United Kingdom
South Tyneside District Hospital
🇬🇧South Shields, United Kingdom
Singleton Hospital
🇬🇧Swansea, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, United Kingdom
Milton Keynes General Hospital
🇬🇧Milton Keynes, Buckinghamshire, United Kingdom
Chelsea and Westminster
🇬🇧London, United Kingdom
The Princess Alexandra Hospital NHS Trust
🇬🇧Harlow, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, United Kingdom