Clinical trial NCT04081428: 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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
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
Lead sponsor: NHS Lothian
Sponsor class: OTHER_GOV
First posted: 2019-09-09
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Measurement of the true rectal wall delivered radiation dose compared to planned dose during the prostate SBRT for each patient
timeFrame: Immediately pre each fraction of SBRT day 1 to 5 and immediately post each fraction of SBRT day 1 to 5
Secondary outcomes:
measure: Measurement of SBRT treatment related acute and late normal tissue toxicity
timeFrame: Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment
measure: Measurement of SBRT treatment related quality of life
timeFrame: Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre, Western General Hospital
state: Mid Lothian
Study officials:
affiliation: NHS Lothian
name: Duncan B McLaren, MBBS
role: PRINCIPAL_INVESTIGATOR
References: