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

March 20, 2024 updated by: NHS Lothian

Using Breath,Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT With RayPilot® Motion Management

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
    • Mid Lothian
      • Edinburgh, Mid Lothian, United Kingdom, EH4 2XU
        • Recruiting
        • Edinburgh Cancer Centre, Western General Hospital
        • Contact:
        • Principal Investigator:
          • Duncan B McLaren, MBBS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 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
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 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
Immediately pre each fraction of SBRT day 1 to 5 and immediately post each fraction of SBRT day 1 to 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment
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)
Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Lothian

Investigators

  • Principal Investigator: Duncan B McLaren, MBBS, NHS Lothian

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2018

Primary Completion (Estimated)

December 11, 2024

Study Completion (Estimated)

January 11, 2026

Study Registration Dates

First Submitted

August 1, 2019

First Submitted That Met QC Criteria

September 4, 2019

First Posted (Actual)

September 9, 2019

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC18048

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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