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

Colorectal Cancer Clinical Trial

— TRACC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04050345
• Other study ID #: CCR4344
• Status: Recruiting
• Start date: December 5, 2016
• Est. completion date: July 31, 2031

Study information

• Verified date: June 2024
• Source: Royal Marsden NHS Foundation Trust
• Contact: Hsiang-Chi Chen, MSc
• Phone: 02086426011
• Email: TRACCStudy[@]rmh.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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)

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 information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: July 31, 2031
• Est. primary completion date: July 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

TRACC Part 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 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 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

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 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

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 CAPOX being administered) as calculated by Cockcroft and Gault equation

• Aspartate aminotransferase/ Alanine aminotransferase levels = 2.5 upper limit of normal

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

6. 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.

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 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

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Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Bronglais Hospital	Aberystwyth
United Kingdom	Stoke Mandeville Hospital	Aylesbury
United Kingdom	Basildon and Thurrock University Hospitals	Basildon
United Kingdom	Basingstoke and North Hampshire Hospitals	Basingstoke
United Kingdom	Bedford Hospital	Bedford
United Kingdom	Royal Blackburn Teaching Hospital	Blackburn
United Kingdom	Pilgrim Hospital	Boston
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Bradford Royal Infirmary	Bradford	West Yorkshire
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Burnley General Teaching Hospital	Burnley
United Kingdom	West Suffolk Hospital	Bury
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Kent and Canterbury Hospital	Canterbury
United Kingdom	North Cumbria University Hospitals	Carlisle
United Kingdom	Glangwili Hospital	Carmarthen
United Kingdom	Epsom and St Helier's Hospitals NHS Trust	Carshalton	Surrey
United Kingdom	Broomfield Hospital	Chelmsford	Essex
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	University Hospitals Coventry & Warwickshire	Coventry
United Kingdom	Leighton Hospital	Crewe
United Kingdom	University Hospital Crosshouse	Crosshouse
United Kingdom	Dorset County Hospital NHS Foundation Trust	Dorchester	Dorset
United Kingdom	Medway NHS Foundation Trust	Gillingham
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	The Princess Alexandra Hospital NHS Trust	Harlow
United Kingdom	Withybush General Hospital	Haverfordwest
United Kingdom	Wycombe Hospital	High Wycombe
United Kingdom	Calderdale and Huddersfield NHS Foundation Trust	Huddersfield
United Kingdom	Airedale General Hospital	Keighley
United Kingdom	Kettering General Hospital	Kettering
United Kingdom	Kingston Hospital Foundation Trust	Kingston Upon Thames
United Kingdom	Forth Valley Royal Hospital	Larbert
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Prince Philip Hospital	Llanelli
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Chelsea and Westminster	London
United Kingdom	Guy's & St Thomas Hospital	London	UK
United Kingdom	North Middlesex University Hospital NHS Trust	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St George's NHS Foundation Trust	London
United Kingdom	The Royal Marsden NHS Foundation Trust - London	London
United Kingdom	Maidstone & Tunbridge Wells NHS Trust	Maidstone
United Kingdom	Christie NHS Foundation Trust	Manchester	Greater Manchester
United Kingdom	Chase Farm Hospital	Middlesex
United Kingdom	Milton Keynes General Hospital	Milton Keynes	Buckinghamshire
United Kingdom	Northampton General Hospital NHS Trust	Northampton
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	George Eliot Hospital	Nuneaton
United Kingdom	Poole Hospital	Poole	Dorset
United Kingdom	Queen Alexandra Hospital	Portsmouth	Hampshire
United Kingdom	Royal Preston Hospital, Lancashire Teaching Hospitals	Preston
United Kingdom	Barking Havering and Redbridge NHS Foundation Trust (Queen's Hospital	Romford
United Kingdom	Salisbury District Hospital	Salisbury	Whiltshire
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury
United Kingdom	South Tyneside District Hospital	South Shields
United Kingdom	University Hospital Southampton	Southampton
United Kingdom	Stockport NHS Foundation Trust	Stockport
United Kingdom	Sunderland Royal Hospital	Sunderland
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United Kingdom	King's Mill Hospital	Sutton In Ashfield
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Musgrove Park Hospital	Taunton	Somerset
United Kingdom	Croydon University Hospital	Thornton Heath	Croydon
United Kingdom	Weston General Hospital	Weston-super-Mare	Somerset
United Kingdom	Wrightington, Wigan and Leigh NHS Foundation Trust	Wigan
United Kingdom	Royal Hampshire County Hospital	Winchester
United Kingdom	University Hospital of South Manchester & Manchester Royal Infirmary	Wythenshawe	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TRACC Part B (Translational sub study)	• 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	6 years
Primary	TRACC Part C (Randomised ctDNA guided adjuvant chemotherapy versus SoC study):	• 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)	4 years
Secondary	Relationship between ctDNA detection before, during and after treatment	To calculate the association between detectable ctDNA with disease free survival and overall survival at four time points during treatment.	8 years