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Transcriptional Responses as an Indicator of Individualised Responses to Radiation Effects (RTGene 2)

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ClinicalTrials.gov Identifier: NCT03809377
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : August 8, 2019
Sponsor:
Collaborator:
Public Health England
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

Brief Summary:
Peripheral blood samples will be taken with informed consent from radiotherapy patients before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head & neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in the literature as being specific to radiation responses will be assessed, together with genes relevant to systemic inflammatory and immune responses, to identify transcriptional responses for a range of doses and exposures on an inter-individual basis. Data will be analysed using existing and new statistical tools focused on count data modelling. The intended outcome is identification of a radiation specific panel of genes to inform individual radiation responses and if the results are favourable, a large scale follow up to this project is expected.

Condition or disease Intervention/treatment
Cancer Procedure: Blood donation during radiotherapy

Detailed Description:

Biomarkers of radiation exposure are recognised to form an important component of the 'toolkit' for initial triage assessment of potentially exposed individuals in a mass casualty radiation accident or incident. Furthermore, radiation is an important medical tool and biomarkers can contribute to longer term assessment of radiation effects and public health risks. The gene expression assay has been gaining popularity as a sensitive biological marker of radiation exposure with the potential to be used for truly individualised dosimetry. The possibility for this assay to be used for a large scale mass-casualty scenario has been proposed and tested in a recent inter-comparison exercise. However, a fuller understanding of genetic factors that contribute to individual radiation risks is needed to inform tailored screening approaches - i.e. to identify a truly radiation specific panel of genetics responses for use as a transcriptional biomarker.

At Columbia University, research has shown that transcriptional effects have the potential to be used as individualised predictors of radiosensitivity to early and late effects. At Public Health England (PHE), recently established molecular counting nCounter technology allows direct counting of nucleic acid molecules (DNA, mRNA, miRNA and lncRNA) without the need for enzymatic reaction or amplification steps hence reducing time for data collection. This new gene expression analysis technique has been assessed for radiation biodosimetry applications with promising results. Furthermore, gene expression has shown a high degree of promise as a marker for late effects of radiation, for instance normal tissue reactions following curative radiotherapy for breast cancer.

In the earlier pilot RTGene study the investigators found genes that are consistently down-regulated and up-regulated towards the end of the radiotherapy treatment. The next stage of this work (RTGene 2) will be to validate the nCounter data for a small number of new genes consistently found in the top 6 of differentially expressed. Importantly, in an attempt to identify genes which are promising biomarkers of susceptibility to radiation-induced toxicity, expression levels will need to be compared with normal tissue reaction to IR, and combined with longer term radiation toxicity data to identify genes with the most pronounced expression level fluctuations during and after radiotherapy.

Peripheral blood samples will be taken with informed consent from radiotherapy patients before and during treatment fractions for sarcoma, breast, lung, gut, genitourinary and head & neck tumours at The Royal Marsden. Candidate genes identified by PHE, Columbia and/or in the literature as being specific to radiation responses will be assessed, together with genes relevant to systemic inflammatory and immune responses, to identify transcriptional responses for a range of doses and exposures on an inter-individual basis. Data will be analysed using existing and new statistical tools focused on count data modelling. The intended outcome is identification of a radiation specific panel of genes to inform individual radiation responses and if the results are favourable, a large scale follow up to this project is expected.


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Study Type : Observational
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Multi-panel Coding and Non-coding Transcriptional Responses as an Indicator of Individualised Responses to Radiation Effects in Radiation Therapy Patients
Actual Study Start Date : May 9, 2019
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2022

Group/Cohort Intervention/treatment
Blood donation during radiotherapy
Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy
Procedure: Blood donation during radiotherapy
Participants will be asked to donate a blood sample at 5 time points during and after radiotherapy




Primary Outcome Measures :
  1. Validation of new transcriptional techniques [ Time Frame: 24 months after all participants have finished radiotherapy and donated blood samples ]
    Using nCounter platform to validate biomarkers of individual radiation exposure, in vivo



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients undergoing radiotherapy for cancer
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • Requirement for external beam radiotherapy (large-field RT) for sarcoma, breast, lung, gastrointestinal, head & neck or genitourinary tumours
  • Written informed consent

Exclusion Criteria:

  • Previous radiotherapy
  • Concurrent chemotherapy/biological therapy or chemotherapy/biological therapy preceding radiotherapy by less than 4 weeks
  • Concurrent hormone therapy or hormone therapy preceding radiotherapy by less than 4 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03809377


Contacts
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Contact: Lone Gothard +44(0)2086613460 lone.gothard@icr.ac.uk
Contact: Sue Boyle +44(0)2086613986 sue.boyle@icr.ac.uk

Locations
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United Kingdom
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Lone Gothard    +442086613460    lone.gothard@icr.ac.uk   
Contact: Sue Boyle    +442086613986    sue.boyle@icr.ac.uk   
Principal Investigator: Navita Somaiah         
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Public Health England
Investigators
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Principal Investigator: Navita Somaiah The Institute of Cancer Research, London, UK

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Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT03809377     History of Changes
Other Study ID Numbers: IRAS258792
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No