Clinical trial NCT01888601: TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx)
Official title: TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Non-small Cell Lung Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2013-06-28
Enrollment: 814
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage I-IIIA NSCLC eligible for primary surgery

Brief summary: 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).

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.

Eligibility criteria: 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surgery (due to the presence of possible nodal involvement on the pre-operative scan) may also be included, but will be withdrawn if post-surgical staging remains IB.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

Primary outcomes:
measure: Intratumour heterogeneity
timeFrame: Year 5
Secondary outcomes:
Other outcomes:
Locations:
city: Harlow
country: United Kingdom
facility: The Princess Alexandra Hospital NHS Trust
state: Essex
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: Select region
city: Chertsey
country: United Kingdom
facility: Ashford and St Peter's Hospitals NHS Foundation Trust
state: Surrey
city: Aberdeen
country: United Kingdom
facility: Grampian Health Board
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow & Clyde
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: North Middlesex University Hospital NHS Trust
city: London
country: United Kingdom
facility: The Whittington Hospital NHS Trust, trading as Whittington Health
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust - Barnet Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Chief Investigator
name: Charles Swanton
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.