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

Overview

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.

Interventions

• Radiation High dose rate prostate brachytherapy
  Temporary implantation of radioactive material into the prostate in the form of a stepping source of Iridium 192 that travels through 16-18 needles or catheters strategically placed through the prostate.

Primary outcome measures

• Changes in biomolecular composition in prostate cancer after high dose rate prostate brachytherapy as measured by Raman spectroscopy [Time frame: 1-2 weeks, PSA: 0-10 years]
• ctDNA detection following HDR Brachytherapy [Time frame: 0-4 weeks]
• Immunogenicity against somatic mutations [Time frame: 0-4 weeks]
• Gut microbiome [Time frame: 0-4 weeks]

Secondary outcome measures (3)

• Response Outcome: PSA Nadir [Time frame: 0-10 years]
• Response Outcome: 4-year PSA [Time frame: 0-4 years]
• Acute and long term toxicity [Time frame: 0-10 years]

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 (< 20) 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• British Columbia Cancer Center for the Southern Interior — Kelowna

Identifiers

NCT: NCT06200974 · H23-02872

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗