Clinical trial NCT06200974: Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer
Official title: Multi-omic Approach to Study High Dose Rate (HDR) Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Localized Prostate Carcinoma
Keywords: Brachytherapy
TRACKS
High Dose Rate
Prostate cancer
favorable risk
intermediate risk
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: BC Cancer Foundation
name: University of British Columbia
name: Vancouver Prostate Centre
First posted: 2024-01-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with localized prostate cancer suitable for brachytherapy as monotherapy.

Brief summary: This is an observational single-center trial for patients with localized prostate cancer suitable for High Dose Rate (HDR) brachytherapy as monotherapy. This study takes a multi-omics approach to study the mechanism of action of HDR brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. The results of this study will clarify the optimal dose for HDR prostate brachytherapy by documenting the dose-response relationship seen in the changing tumor metabolites after HDR brachytherapy and investigate the immunogenicity of HDR brachytherapy.

Detailed description: High Dose Rate (HDR) prostate brachytherapy is an effective and highly conformal means of delivering curative radiation to the prostate. Because of the high dose rate, initial studies applied this treatment cautiously in multiple sessions or fractions but this has gradually been reduced from 54 Gy in 9 fractions to 42 Gy in 6, then 36 Gy in 3, then 27 Gy in 2 and finally to one single fraction of 19 Gy. Each change in fractionation was calculated to be equivalent to the previous, and remarkably, efficacy was maintained until the final stage when treatment was reduced to a single fraction. This resulted in a significant drop in cure rates from over 90% to approximately 65%. The investigators assume that the prior fractions served to sensitize the tumor to subsequent radiation; however, this remains an open question.

This observational single-center trial for localized prostate cancer suitable for brachytherapy as monotherapy takes a novel multi-omics approach to study the mechanism of action of High Dose Rate (HDR) brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. This is achieved through (1) measurement of changes in metabolites as determined by Raman spectroscopy, (2) analysis of circulating tumor DNA in peripheral blood plasma, (3) evaluation of the changes in immune response by single cell RNA (scRNA)-sequencing, and (4) evaluation of gut microbiome composition before and after treatment. Secondary endpoints of the study include PSA nadir, time to nadir, PSA at 4 years and patterns of failure.

The study will enroll 100 men with localized prostate cancer suitable for brachytherapy as monotherapy. HDR brachytherapy is given in 2 fractions, each one under anesthesia, making it possible to obtain biopsies painlessly at both baseline prior to any treatment, and 1-2 weeks later prior to the second half of treatment. The results of this study will clarify the dose-response relationship for HDR brachytherapy, help to define the optimal dose, clarify the metabolic response to HDR brachytherapy, and investigate the potential immunogenicity of HDR brachytherapy.

Eligibility criteria: Inclusion Criteria:

* Favorable risk and intermediate-risk prostate cancer with estimated life expectancy of at least 10 years.
* Clinical stage T1c-T2b, PSA \< 20, Gleason \< 8
* ECOG 0-1
* Low tier intermediate-risk prostate cancer is defined by: a single NCCN intermediate risk factor (either Gleason 7(3+4) and PSA \< 10 ng/ml OR Gleason 6 and PSA 10-20 ng/ml)
* Extensive favorable-risk disease is defined as: clinical stage T1c-T2a, PSA \< 10, Gleason 6, ≥ 50% of biopsy cores containing cancer, PSA density \> 0.2 ng/cc,
* Selected intermediate risk patients not defined above

  * T1c/T2a
  * PSA \< 10 and Gleason 4+3
  * PSA \> 10 and Gleason 3+4
  * PSA 10-15 ng/ml and Gleason 4+3 and \< 33% cores involved
  * Max tumor length in any core 10 mm
* No androgen deprivation therapy (ADT)
* Signed study specific informed consent.

Exclusion Criteria:

* Prior radical surgery for carcinoma of the prostate,
* Prior pelvic radiation
* Prior chemotherapy for prostate cancer,
* Claustrophobic or unable to undergo MRI
* Patients unsuitable for general anesthesia, on blood thinners which cannot be stopped for 24 hours, or who have contraindications to radiotherapy such as systemic sclerosis, or inflammatory bowel disease

Primary outcomes:
measure: Changes in biomolecular composition in prostate cancer after high dose rate prostate brachytherapy as measured by Raman spectroscopy
timeFrame: 1-2 weeks, PSA: 0-10 years
measure: ctDNA detection following HDR Brachytherapy
timeFrame: 0-4 weeks
measure: Immunogenicity against somatic mutations
timeFrame: 0-4 weeks
measure: Gut microbiome
timeFrame: 0-6 weeks
Secondary outcomes:
measure: Response Outcome: PSA Nadir
timeFrame: 0-10 years
measure: Response Outcome: 4-year PSA
timeFrame: 0-4 years
measure: Acute and long term toxicity
timeFrame: 0-10 years
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: British Columbia Cancer Center for the Southern Interior
state: British Columbia
Study officials:
affiliation: Radiation Oncologist
name: Juanita M Crook, MD
role: PRINCIPAL_INVESTIGATOR
References: