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

NCT ID: NCT04050345

Last Updated: 2024-06-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-12-05

Study Completion Date

2031-07-31

Brief Summary

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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

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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.

Conditions

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Colorectal Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Part B TRACC Colon

Patients with diagnosis of large bowel cancer (in the colon) and no evidence of metastatic disease

No interventions assigned to this group

Part B TRACC Rectal

Patients who have a diagnosis of large bowel cancer (in the Rectum) and no evidence of metastatic disease

No interventions assigned to this group

Part C TRACC- Standard of Care Adjuvant Chemotherapy

Randomised to Arm A: Standard of Care Arm (Patients with fully resected high risk stage II or stage III colon or Rectal cancer with no evidence of metastatic disease. Patients with locally advanced rectal cancer who have previously undergone chemoradiotherapy are also eligible to enrol.

No interventions assigned to this group

Part C-ct DNA Guided Arm

Patients with fully resected high risk stage II or stage III colon or rectal cancer with no evidence of metastatic disease. Patients with locally advanced rectal cancer who have previously undergone chemoradiotherapy are also eligible to enrol.

De-escalation of adjuvant chemotherapy in patients who have a post-operative ctDNA negative result

No interventions assigned to this group

Eligibility Criteria

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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


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

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


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

\-
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Cunningham

Role: STUDY_CHAIR

Royal Marsden NHS Foundation Trust

Locations

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Milton Keynes General Hospital

Milton Keynes, Buckinghamshire, United Kingdom

Site Status RECRUITING

Croydon University Hospital

Thornton Heath, Croydon, United Kingdom

Site Status RECRUITING

Dorset County Hospital NHS Foundation Trust

Dorchester, Dorset, United Kingdom

Site Status RECRUITING

Poole Hospital

Poole, Dorset, United Kingdom

Site Status RECRUITING

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Site Status RECRUITING

Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Site Status RECRUITING

Queen Alexandra Hospital

Portsmouth, Hampshire, United Kingdom

Site Status RECRUITING

University Hospital of South Manchester & Manchester Royal Infirmary

Wythenshawe, Manchester, United Kingdom

Site Status RECRUITING

Musgrove Park Hospital

Taunton, Somerset, United Kingdom

Site Status RECRUITING

Weston General Hospital

Weston-super-Mare, Somerset, United Kingdom

Site Status RECRUITING

Epsom and St Helier's Hospitals NHS Trust

Carshalton, Surrey, United Kingdom

Site Status ACTIVE_NOT_RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Site Status RECRUITING

Guy's & St Thomas Hospital

London, UK, United Kingdom

Site Status RECRUITING

Bradford Royal Infirmary

Bradford, West Yorkshire, United Kingdom

Site Status RECRUITING

Salisbury District Hospital

Salisbury, Whiltshire, United Kingdom

Site Status RECRUITING

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status RECRUITING

Bronglais Hospital

Aberystwyth, , United Kingdom

Site Status RECRUITING

Stoke Mandeville Hospital

Aylesbury, , United Kingdom

Site Status RECRUITING

Basildon and Thurrock University Hospitals

Basildon, , United Kingdom

Site Status RECRUITING

Basingstoke and North Hampshire Hospitals

Basingstoke, , United Kingdom

Site Status RECRUITING

Bedford Hospital

Bedford, , United Kingdom

Site Status RECRUITING

Royal Blackburn Teaching Hospital

Blackburn, , United Kingdom

Site Status RECRUITING

Pilgrim Hospital

Boston, , United Kingdom

Site Status RECRUITING

Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Site Status RECRUITING

University Hospitals Bristol NHS Foundation Trust

Bristol, , United Kingdom

Site Status RECRUITING

Burnley General Teaching Hospital

Burnley, , United Kingdom

Site Status RECRUITING

West Suffolk Hospital

Bury, , United Kingdom

Site Status RECRUITING

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Kent and Canterbury Hospital

Canterbury, , United Kingdom

Site Status RECRUITING

North Cumbria University Hospitals

Carlisle, , United Kingdom

Site Status RECRUITING

Glangwili Hospital

Carmarthen, , United Kingdom

Site Status RECRUITING

Castle Hill Hospital

Cottingham, , United Kingdom

Site Status RECRUITING

University Hospitals Coventry & Warwickshire

Coventry, , United Kingdom

Site Status RECRUITING

Leighton Hospital

Crewe, , United Kingdom

Site Status RECRUITING

University Hospital Crosshouse

Crosshouse, , United Kingdom

Site Status RECRUITING

Medway NHS Foundation Trust

Gillingham, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status RECRUITING

The Princess Alexandra Hospital NHS Trust

Harlow, , United Kingdom

Site Status RECRUITING

Withybush General Hospital

Haverfordwest, , United Kingdom

Site Status RECRUITING

Wycombe Hospital

High Wycombe, , United Kingdom

Site Status RECRUITING

Calderdale and Huddersfield NHS Foundation Trust

Huddersfield, , United Kingdom

Site Status RECRUITING

Airedale General Hospital

Keighley, , United Kingdom

Site Status RECRUITING

Kettering General Hospital

Kettering, , United Kingdom

Site Status RECRUITING

Kingston Hospital Foundation Trust

Kingston upon Thames, , United Kingdom

Site Status RECRUITING

Forth Valley Royal Hospital

Larbert, , United Kingdom

Site Status RECRUITING

St James's University Hospital

Leeds, , United Kingdom

Site Status RECRUITING

Lincoln County Hospital

Lincoln, , United Kingdom

Site Status RECRUITING

Prince Philip Hospital

Llanelli, , United Kingdom

Site Status RECRUITING

Barts Health NHS Trust

London, , United Kingdom

Site Status RECRUITING

North Middlesex University Hospital NHS Trust

London, , United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

St George's NHS Foundation Trust

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

The Royal Marsden NHS Foundation Trust - London

London, , United Kingdom

Site Status RECRUITING

Chelsea and Westminster

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Maidstone & Tunbridge Wells NHS Trust

Maidstone, , United Kingdom

Site Status RECRUITING

Chase Farm Hospital

Middlesex, , United Kingdom

Site Status RECRUITING

Northampton General Hospital NHS Trust

Northampton, , United Kingdom

Site Status RECRUITING

Nottingham University Hospital

Nottingham, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

George Eliot Hospital

Nuneaton, , United Kingdom

Site Status RECRUITING

Royal Preston Hospital, Lancashire Teaching Hospitals

Preston, , United Kingdom

Site Status RECRUITING

Barking Havering and Redbridge NHS Foundation Trust (Queen's Hospital

Romford, , United Kingdom

Site Status RECRUITING

Weston Park Hospital

Sheffield, , United Kingdom

Site Status RECRUITING

Royal Shrewsbury Hospital

Shrewsbury, , United Kingdom

Site Status RECRUITING

South Tyneside District Hospital

South Shields, , United Kingdom

Site Status RECRUITING

University Hospital Southampton

Southampton, , United Kingdom

Site Status RECRUITING

Stockport NHS Foundation Trust

Stockport, , United Kingdom

Site Status RECRUITING

Sunderland Royal Hospital

Sunderland, , United Kingdom

Site Status RECRUITING

King's Mill Hospital

Sutton in Ashfield, , United Kingdom

Site Status RECRUITING

Singleton Hospital

Swansea, , United Kingdom

Site Status RECRUITING

Wrightington, Wigan and Leigh NHS Foundation Trust

Wigan, , United Kingdom

Site Status RECRUITING

Royal Hampshire County Hospital

Winchester, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Hsiang-Chi Chen, MSc

Role: CONTACT

02086426011

Susie Slater, Dr

Role: CONTACT

Facility Contacts

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Sarah Duff

Role: primary

Graham Branagan

Role: primary

Venkatesh Gajapathy

Role: primary

References

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Slater S, Bryant A, Aresu M, Begum R, Chen HC, Peckitt C, Lazaro-Alcausi R, Carter P, Anandappa G, Khakoo S, Melcher L, Potter V, Marti FM, Huang J, Branagan G, George N, Abulafi M, Duff S, Raja A, Gupta A, West N, Bucheit L, Rich T, Chau I, Cunningham D, Starling N; TRACC Part B trial investigators. Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study. Clin Cancer Res. 2024 Aug 15;30(16):3459-3469. doi: 10.1158/1078-0432.CCR-24-0226.

Reference Type DERIVED
PMID: 38864835 (View on PubMed)

Slater S, Bryant A, Chen HC, Begum R, Rana I, Aresu M, Peckitt C, Zhitkov O, Lazaro-Alcausi R, Borja V, Powell R, Lowery D, Hubank M, Rich T, Anandappa G, Chau I, Starling N, Cunningham D. ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C). BMC Cancer. 2023 Mar 20;23(1):257. doi: 10.1186/s12885-023-10699-4.

Reference Type DERIVED
PMID: 36941575 (View on PubMed)

Other Identifiers

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CCR4344

Identifier Type: -

Identifier Source: org_study_id

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