TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx) (TRACERx)

To study the NSCLC evolutionary genomic landscape between primary and metastatic sites and the dynamics of intratumour heterogeneity over time combined with detailed clinical, histopathological and cancer phenotypic annotation for each patient, in order to significantly improve the outcomes of NSCLC patients (e.g. reduce their chance of recurrence and improve survival).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer

Detailed Description

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

• Study Type: Observational
• Enrollment (Actual): 814

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB15 6RE
    • Grampian Health Board
  • Birmingham, United Kingdom, B9 5SS
    • Heart of England NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 4XW
    • Cardiff And Vale University Health Board
  • Glasgow, United Kingdom
    • NHS Greater Glasgow & Clyde
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS Trust
  • Liverpool, United Kingdom
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton & Harefield NHS Foundation Trust
  • London, United Kingdom, N18 1QX
    • North Middlesex University Hospital NHS Trust
  • London, United Kingdom, E1 1RD
    • Barts Health NHS Trust
  • London, United Kingdom, N19 5NF
    • The Whittington Hospital NHS Trust, trading as Whittington Health
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust - Barnet Hospital
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester NHS Foundation Trust
  • Sheffield, United Kingdom, S5 7AU
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Essex
    • Harlow, Essex, United Kingdom, CM20 1QX
      • The Princess Alexandra Hospital NHS Trust
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust
  • Select Region
    • London, Select Region, United Kingdom, NW1 2PG
      • University College London Hospitals Nhs Foundation Trust
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Ashford and St Peter's Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage I-IIIA NSCLC eligible for primary surgery

Description

Inclusion Criteria:

• Written Informed consent
• Patients ≥18 years of age, with early stage IIA-IIIB disease (according to TNM 8th edition) who are eligible for primary surgery. Patients with a radiological staging of IB (N0) who could be upstaged to IIA-IIIB following surgery (due to the presence of possible nodal involvement on the pre-operative scan) may also be included, but will be withdrawn if post-surgical staging remains IB.

Histopathologically confirmed NSCLC, or a strong suspicion of cancer on lung imaging necessitating surgery (e.g. diagnosis determined from frozen section in theatre)

• Primary surgery in keeping with NICE guidelines planned (see section 9.3)
• Agreement to be followed up at a TRACERx site
• Performance status 0 or 1
• Minimum tumour diameter at least 15mm to allow for sampling of at least two tumour regions (if 15mm, a high likelihood of nodal involvement on pre-operative imaging required to meet eligibility according to stage, i.e. T1N1-3)

Exclusion Criteria:

• Any other* malignancy diagnosed or relapsed at any time, which is currently being treated (including by hormonal therapy).

• Any other* current malignancy or malignancy diagnosed or relapsed within the past 3 years**.

  *Exceptions are: non-melanomatous skin cancer, stage 0 melanoma in situ, and in situ cervical cancer

  **An exception will be made for malignancies diagnosed or relapsed more than 2, but less than 3, years ago only if a pre-operative biopsy of the lung lesion has confirmed a diagnosis of NSCLC.

• Psychological condition that would preclude informed consent
• Treatment with neo-adjuvant therapy for current lung malignancy deemed necessary
• Post-surgery staging is not IIA-IIIB
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or syphilis infection.
• Sufficient tissue, i.e. a minimum of two tumour regions, is unlikely to be obtained for the study based on pre-operative imaging

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NSCLC eligible for primary surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intratumour heterogeneity	• Define the relationship between intratumour heterogeneity and clinical outcome following surgery and adjuvant therapy (including relationships between intratumour heterogeneity and clinical disease stage and histological subtypes of NSCLC).	Year 5

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Cancer Research UK
• Investigators: Principal Investigator: Charles Swanton, Chief Investigator

Publications and helpful links

General Publications

• AbdulJabbar K, Raza SEA, Rosenthal R, Jamal-Hanjani M, Veeriah S, Akarca A, Lund T, Moore DA, Salgado R, Al Bakir M, Zapata L, Hiley CT, Officer L, Sereno M, Smith CR, Loi S, Hackshaw A, Marafioti T, Quezada SA, McGranahan N, Le Quesne J; TRACERx Consortium; Swanton C, Yuan Y. Geospatial immune variability illuminates differential evolution of lung adenocarcinoma. Nat Med. 2020 Jul;26(7):1054-1062. doi: 10.1038/s41591-020-0900-x. Epub 2020 May 27.
• Hynds RE, Ben Aissa A, Gowers KHC, Watkins TBK, Bosshard-Carter L, Rowan AJ, Veeriah S, Wilson GA, Quezada SA, Swanton C; TRACERx Consortium; Janes SM. Expansion of airway basal epithelial cells from primary human non-small cell lung cancer tumors. Int J Cancer. 2018 Jul 1;143(1):160-166. doi: 10.1002/ijc.31383. Epub 2018 Apr 6.
• Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, Shafi S, Johnson DH, Mitter R, Rosenthal R, Salm M, Horswell S, Escudero M, Matthews N, Rowan A, Chambers T, Moore DA, Turajlic S, Xu H, Lee SM, Forster MD, Ahmad T, Hiley CT, Abbosh C, Falzon M, Borg E, Marafioti T, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Shah R, Joseph L, Quinn AM, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Dentro S, Taniere P, O'Sullivan B, Lowe HL, Hartley JA, Iles N, Bell H, Ngai Y, Shaw JA, Herrero J, Szallasi Z, Schwarz RF, Stewart A, Quezada SA, Le Quesne J, Van Loo P, Dive C, Hackshaw A, Swanton C; TRACERx Consortium. Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 1;376(22):2109-2121. doi: 10.1056/NEJMoa1616288. Epub 2017 Apr 26.
• Bernatz S, Prudente V, Pai S, Attermann AK, Di Federico A, Rowan A, Veeriah S, Dyrskjot L, Nurnberg L, Alessi JV, Ott PA, Sharon E, Hackshaw A, McGranahan N, Abbosh C, Mak RH, Bitterman D, Awad M, Ricciuti B, Swanton C, Jamal-Hanjani M, Birkbak NJ, Aerts HJWL. Thymic health and immunotherapy outcomes in patients with cancer. Nature. 2026 Apr;652(8111):995-1003. doi: 10.1038/s41586-026-10243-x. Epub 2026 Mar 18.
• Biswas D, Liu YH, Herrero J, Wu Y, Moore DA, Karasaki T, Grigoriadis K, Lu WT, Veeriah S, Naceur-Lombardelli C, Magno N, Ward S, Frankell AM, Hill MS, Colliver E, de Carne Trecesson S, East P, Malhi A, Snell DM, O'Neill O, Leonce D, Mattsson J, Lindberg A, Micke P, Moldvay J, Megyesfalvi Z, Dome B, Fillinger J, Nicod J, Downward J, Szallasi Z; TRACERx Consortium; Hackshaw A, Jamal-Hanjani M, Kanu N, Birkbak NJ, Swanton C. Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma. Nat Cancer. 2025 Jan;6(1):86-101. doi: 10.1038/s43018-024-00883-1. Epub 2025 Jan 9.
• Pan X, AbdulJabbar K, Coelho-Lima J, Grapa AI, Zhang H, Cheung AHK, Baena J, Karasaki T, Wilson CR, Sereno M, Veeriah S, Aitken SJ, Hackshaw A, Nicholson AG, Jamal-Hanjani M; TRACERx Consortium; Swanton C, Yuan Y, Le Quesne J, Moore DA. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma. Nat Cancer. 2024 Feb;5(2):347-363. doi: 10.1038/s43018-023-00694-w. Epub 2024 Jan 10.
• Abbosh C, Frankell AM, Harrison T, Kisistok J, Garnett A, Johnson L, Veeriah S, Moreau M, Chesh A, Chaunzwa TL, Weiss J, Schroeder MR, Ward S, Grigoriadis K, Shahpurwalla A, Litchfield K, Puttick C, Biswas D, Karasaki T, Black JRM, Martinez-Ruiz C, Bakir MA, Pich O, Watkins TBK, Lim EL, Huebner A, Moore DA, Godin-Heymann N, L'Hernault A, Bye H, Odell A, Kalavakur P, Gomes F, Patel AJ, Manzano E, Hiley CT, Carey N, Riley J, Cook DE, Hodgson D, Stetson D, Barrett JC, Kortlever RM, Evan GI, Hackshaw A, Daber RD, Shaw JA, Aerts HJWL, Licon A, Stahl J, Jamal-Hanjani M; TRACERx Consortium; Birkbak NJ, McGranahan N, Swanton C. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA. Nature. 2023 Apr;616(7957):553-562. doi: 10.1038/s41586-023-05776-4. Epub 2023 Apr 13.
• Frankell AM, Dietzen M, Al Bakir M, Lim EL, Karasaki T, Ward S, Veeriah S, Colliver E, Huebner A, Bunkum A, Hill MS, Grigoriadis K, Moore DA, Black JRM, Liu WK, Thol K, Pich O, Watkins TBK, Naceur-Lombardelli C, Cook DE, Salgado R, Wilson GA, Bailey C, Angelova M, Bentham R, Martinez-Ruiz C, Abbosh C, Nicholson AG, Le Quesne J, Biswas D, Rosenthal R, Puttick C, Hessey S, Lee C, Prymas P, Toncheva A, Smith J, Xing W, Nicod J, Price G, Kerr KM, Naidu B, Middleton G, Blyth KG, Fennell DA, Forster MD, Lee SM, Falzon M, Hewish M, Shackcloth MJ, Lim E, Benafif S, Russell P, Boleti E, Krebs MG, Lester JF, Papadatos-Pastos D, Ahmad T, Thakrar RM, Lawrence D, Navani N, Janes SM, Dive C, Blackhall FH, Summers Y, Cave J, Marafioti T, Herrero J, Quezada SA, Peggs KS, Schwarz RF, Van Loo P, Miedema DM, Birkbak NJ, Hiley CT, Hackshaw A, Zaccaria S; TRACERx Consortium; Jamal-Hanjani M, McGranahan N, Swanton C. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature. 2023 Apr;616(7957):525-533. doi: 10.1038/s41586-023-05783-5. Epub 2023 Apr 12.
• Al Bakir M, Huebner A, Martinez-Ruiz C, Grigoriadis K, Watkins TBK, Pich O, Moore DA, Veeriah S, Ward S, Laycock J, Johnson D, Rowan A, Razaq M, Akther M, Naceur-Lombardelli C, Prymas P, Toncheva A, Hessey S, Dietzen M, Colliver E, Frankell AM, Bunkum A, Lim EL, Karasaki T, Abbosh C, Hiley CT, Hill MS, Cook DE, Wilson GA, Salgado R, Nye E, Stone RK, Fennell DA, Price G, Kerr KM, Naidu B, Middleton G, Summers Y, Lindsay CR, Blackhall FH, Cave J, Blyth KG, Nair A, Ahmed A, Taylor MN, Procter AJ, Falzon M, Lawrence D, Navani N, Thakrar RM, Janes SM, Papadatos-Pastos D, Forster MD, Lee SM, Ahmad T, Quezada SA, Peggs KS, Van Loo P, Dive C, Hackshaw A, Birkbak NJ, Zaccaria S; TRACERx Consortium; Jamal-Hanjani M, McGranahan N, Swanton C. The evolution of non-small cell lung cancer metastases in TRACERx. Nature. 2023 Apr;616(7957):534-542. doi: 10.1038/s41586-023-05729-x. Epub 2023 Apr 12.
• Ng KW, Boumelha J, Enfield KSS, Almagro J, Cha H, Pich O, Karasaki T, Moore DA, Salgado R, Sivakumar M, Young G, Molina-Arcas M, de Carne Trecesson S, Anastasiou P, Fendler A, Au L, Shepherd STC, Martinez-Ruiz C, Puttick C, Black JRM, Watkins TBK, Kim H, Shim S, Faulkner N, Attig J, Veeriah S, Magno N, Ward S, Frankell AM, Al Bakir M, Lim EL, Hill MS, Wilson GA, Cook DE, Birkbak NJ, Behrens A, Yousaf N, Popat S, Hackshaw A; TRACERx Consortium; CAPTURE Consortium; Hiley CT, Litchfield K, McGranahan N, Jamal-Hanjani M, Larkin J, Lee SH, Turajlic S, Swanton C, Downward J, Kassiotis G. Antibodies against endogenous retroviruses promote lung cancer immunotherapy. Nature. 2023 Apr;616(7957):563-573. doi: 10.1038/s41586-023-05771-9. Epub 2023 Apr 12.
• Martinez-Ruiz C, Black JRM, Puttick C, Hill MS, Demeulemeester J, Larose Cadieux E, Thol K, Jones TP, Veeriah S, Naceur-Lombardelli C, Toncheva A, Prymas P, Rowan A, Ward S, Cubitt L, Athanasopoulou F, Pich O, Karasaki T, Moore DA, Salgado R, Colliver E, Castignani C, Dietzen M, Huebner A, Al Bakir M, Tanic M, Watkins TBK, Lim EL, Al-Rashed AM, Lang D, Clements J, Cook DE, Rosenthal R, Wilson GA, Frankell AM, de Carne Trecesson S, East P, Kanu N, Litchfield K, Birkbak NJ, Hackshaw A, Beck S, Van Loo P, Jamal-Hanjani M; TRACERx Consortium; Swanton C, McGranahan N. Genomic-transcriptomic evolution in lung cancer and metastasis. Nature. 2023 Apr;616(7957):543-552. doi: 10.1038/s41586-023-05706-4. Epub 2023 Apr 12.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Estimated): November 1, 2035
• Study Completion (Estimated): November 1, 2035

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (Estimated): June 28, 2013

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: UCL/12/0279