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

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

Tracking Information

• First Submitted Date: August 1, 2019
• First Posted Date: September 9, 2019
• Last Update Posted Date: March 21, 2024
• Actual Study Start Date: October 11, 2018
• Estimated Primary Completion Date: December 11, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2019)

• 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.
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 4, 2019)

• 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
• 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Using Breath, Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT
• 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
• 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.
• 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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

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.

• 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

Condition

• Prostate Cancer
• Radiotherapy Side Effects
• Volatile Organic Compounds
• DNA Damage

Intervention

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®

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 4, 2019): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 11, 2026
• Estimated Primary Completion Date: December 11, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: men with prostate cancer

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04081428
• Other Study ID Numbers: AC18048
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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

• Current Responsible Party: NHS Lothian
• Original Responsible Party: Same as current
• Current Study Sponsor: NHS Lothian
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: NHS Lothian
• Verification Date: March 2024