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

NCT04081428 | Active Not Recruiting DMC

• 1 other identifier: AC18048
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Prostate cancer; Cell free DNA; Volatile organic compounds; Stereotactic Body Radiotherapy; Radiotherapy side effects; Imaging biomarkers

Outcome Measures

Primary Outcomes (3)

• 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)

  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)

  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

  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 Outcomes (2)

• Measurement of SBRT treatment related acute and late normal tissue toxicity

  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

  Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment

Interventions

Stereotactic Body Radiotherapy RADIATION

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

Also known as: Breath Analysis, Cell-free DNA, Imaging biomarkers, Treatment image guidance with the RayPilot®

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: men with prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• Inflammatory bowel disease
• Previous androgen deprivation therapy
• History of urinary retention

Sponsors & Collaborators

• NHS Lothian: lead

Study Sites (1)

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Mid Lothian, EH4 2XU, United Kingdom

Location

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.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiosurgery; Cell-Free Nucleic Acids

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Duncan B McLaren, MBBS

  NHS Lothian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: September 9, 2019
• Study Start: October 11, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)