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Using Breath, Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT (PRINToUT)

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ClinicalTrials.gov Identifier: NCT04081428
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : March 21, 2024
Sponsor:
Information provided by (Responsible Party):
NHS Lothian

Study Description
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Brief Summary:
Personalisation of radiotherapy dose based on real-time assessments of normal tissue and tumour response would maximise cure and minimise treatment related toxicity. During a 5 fraction course of prostate Stereotactic Body Radiotherapy (SBRT) this pilot study will assess whether a number of different biomarker approaches can predict for normal tissue and tumour response. Firstly the investigators will analyse volatile organic compounds released within the breath with each fraction of treatment. Secondly the investigators will analyse cell free normal tissue and tumour DNA released during treatment. Thirdly the investigators will develop imaging processing algorithms to look for imaging biomarkers predicting rectal wall toxicity using pre and post treatment cone beam CT verification images. Each of these approaches will be assessed against prostate specific antigen (PSA), Common Terminology Criteria for Adverse Events (CTCAE v4.0) criteria and Expanded Prostate Cancer Index Composite (EPIC-26) patient reported outcomes with a maximum of 24 months of follow up.

Condition or disease Intervention/treatment
Prostate Cancer Radiotherapy Side Effects Volatile Organic Compounds DNA Damage Radiation: Stereotactic Body Radiotherapy

Detailed Description:
Radiotherapy scheduling and prescription dose does not take into account individual patient heterogeneity in normal tissue response or tumour response. Personalisation of radiotherapy dose based on real-time assessments of normal tissue and tumour response would maximise cure and minimise treatment related toxicity. During a 5 fraction course of prostate Stereotactic Body Radiotherapy (SBRT) this pilot study will assess whether a number of different biomarker approaches can predict for normal tissue and tumour response. Firstly the investigators will analyse volatile organic compounds released within the breath with each fraction of treatment using Gas Chromatography Ion Mobility Spectroscopy (GC-IMS). The investigators have extensive experience in this area within the TOXI-Triage research program (www.toxi-triage.eu/) including deep learning and machine learning techniques to interrogate the metabolomics data generated. Secondly the investigators will analyse cell free normal tissue and tumour DNA released during treatment to assess both tumour and normal tissue response. Radiotherapy releases large amounts in to the blood stream allowing easier quantitative analysis. Thirdly the investigators will look for imaging biomarkers of rectal wall toxicity using imaging analysis algorithms of on-treatment cone beam verification CT images taken before and after each radiotherapy treatment. The RayPilot® system made by Micropos Medical Ltd tracks prostate motion throughout the SBRT delivery to ensure that the treatment dose is delivered with great precision. The potential of each biomarker approach for predicting normal tissue and tumour response will be assessed against PSA and CTCAE v 4.0 toxicity criteria and EPIC-26 patient reported outcome measures after 24 months of patient follow up.
Study Design
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Study Type : Observational
Estimated Enrollment : 12 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Using Breath,Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT With RayPilot® Motion Management
Actual Study Start Date : October 11, 2018
Estimated Primary Completion Date : December 11, 2024
Estimated Study Completion Date : January 11, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Groups and Cohorts
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Intervention Details:
  • Radiation: Stereotactic Body Radiotherapy
    Daily collection of breath and blood before and after each of the 5 radiotherapy treatment sessions. Before and after daily cone beam CT image collection
    Other Names:
    • Breath Analysis
    • Cell-free DNA
    • Imaging biomarkers
    • Treatment image guidance with the RayPilot®

Outcome Measures
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Primary Outcome Measures :
  1. Measurement of the relative change in Gas Chromatography Ion Mobility Spectra (GC-IMS) of Volatile Organic Compounds (VOC's) from breath samples of men with prostate cancer treated with prostate stereotactic body radiotherapy (SBRT) [ Time Frame: pre treatment before each fraction of SBRT day 1 to day 5, then at 1 and 3 hours post treatment day 1 to day 5 ]
    Measurement of the change in the 3D chromatogram of volatile organic compound GC-IMS Spectra detected from baseline pre-treatment, to completion of SBRT at each time point, for each patient. Each 3D chromatogram GC-IMS printout is generated from the readings of each axis. The y axis is associated with GC separation of VOC's, the x axis measures the movement of the generated ions (IMS drift time) and the z axis ion detector response equating to concentration. These 3 values separate, identify and quantify the VOC compounds detected.

  2. Measurement of the relative change in normal tissue and tumour cell free DNA (cfDNA) released into the blood of men with prostate cancer treated with prostate stereotactic body radiotherapy (SBRT) [ Time Frame: pre treatment before each fraction of SBRT day 1 to day 5, then at 1 and 3 hours post treatment day 1 to day 5 ]
    Change in the density of 90-150 base pair fragment size cfDNA from baseline pre-treatment to completion of SBRT for each time point, for each patient

  3. Measurement of the true rectal wall delivered radiation dose compared to planned dose during the prostate SBRT for each patient [ Time Frame: Immediately pre each fraction of SBRT day 1 to 5 and immediately post each fraction of SBRT day 1 to 5 ]
    Dose calculation in cGy between expected and observed actual dose to the rectal wall using pre and post each fraction radiotherapy linear accelerator treatment verification cone beam CT scans


Secondary Outcome Measures :
  1. Measurement of SBRT treatment related acute and late normal tissue toxicity [ Time Frame: Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment ]
    Common Terminology Criteria for Adverse Events CTCAE v 4.0 scores for urinary and bowel treatment related toxicity. Scale runs form Grade 1 mild requiring no intervention to grade 5 death

  2. Measurement of SBRT treatment related quality of life [ Time Frame: Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment ]
    Expanded Prostate Cancer Index Composite EPIC-26 patient reported outcomes questionnaire. A clinical tool to assess urinary, bowel, sexual and vitality health. The score from each of the 5 domains runs from 0 (none) to 12 (severe) impact on quality of life. Each domain score when added together gives an overall score of zero (unaffected) to 60 (severely affected)


Biospecimen Retention:   Samples With DNA
Volatile Organic Compound Breath Analysis, Cell-Free DNA normal tissue and tumour DNA, Cone Beam CT pre and post each fraction of radiotherapy, Genomic saliva analysis.

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   men with prostate cancer
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Men diagnosed with localised prostate cancer within the South East of Scotland cancer network who are suitable for study entry
Criteria

Inclusion Criteria:

  • Low risk prostate cancer T1-2, PSA<10ng/ml, Gleason score (GS) 3+3=6
  • Intermediate risk prostate cancer T1-T2, PSA 10-20ng/ml,GS ≤7(3+4=7 only)
  • World Health Organisation (WHO) performance status 0-2
  • Prostate volume ≤90cc
  • International Prostate Symptom Score (IPSS) ≤20
  • Peak urinary flow rate (Q-max) >10cc/sec
  • Urinary residual <250mls total
  • No prior Trans Urethral Resection of the Prostate (TURP)
  • No previous pelvic radiotherapy
  • Able to give informed consent
  • Aged between 18-85 years of age

Exclusion Criteria:

  • Inflammatory bowel disease
  • Previous androgen deprivation therapy
  • History of urinary retention
Contacts and Locations
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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): NCT04081428


Contacts
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Contact: Susan Forman +44 131 537 1000 ext 3253 susan.forman@luht.scot.nhs.uk

Locations
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United Kingdom
Edinburgh Cancer Centre, Western General Hospital Recruiting
Edinburgh, Mid Lothian, United Kingdom, EH4 2XU
Contact: Susan Forman    +44 131 537 1000 ext 3253    susan.forman@luht.scot.nhs.uk   
Principal Investigator: Duncan B McLaren, MBBS         
Sponsors and Collaborators
NHS Lothian
Investigators
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Principal Investigator: Duncan B McLaren, MBBS NHS Lothian
More Information
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Responsible Party: NHS Lothian
ClinicalTrials.gov Identifier: NCT04081428    
Other Study ID Numbers: AC18048
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: March 21, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The pilot data will be used to inform a larger study cohort and to establish the optimal methodology and time points for sample collection

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NHS Lothian:
Prostate cancer
Cell free DNA
Volatile organic compounds
 Stereotactic Body Radiotherapy
Radiotherapy side effects
Imaging biomarkers
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
 Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases