Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT) (IMPRINT)

Intestinal Microbiota in Prostate Cancer Patients as a Biomarker for Radiation-INduced Toxicity (IMPRINT): A Prospective Biomarker Study

Radiotherapy (RT) of the abdomen and/or pelvis is known to cause acute and late gastrointestinal (GI) toxicities. While radiation dose and volume are known risk factors for developing such side effects, recent evidence suggests patterns of disturbance in the composition of the GI microbiota - so called "dysbiosis" - may also promote the host's susceptibility to GI toxicities through impaired intestinal barrier function and inflammation. The IMPRINT-study aims to expand the current knowledge on the role of intestinal bacteria and their metabolites involved in the pathophysiology of radiation-induced GI toxicities by longitudinally examining the microbiota composition (feces), the associated metabolome (blood, feces and urine) and bacterial extracellular vesicles (BEVs) (blood and feces).

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms; Prostate Cancer; Prostate Adenocarcinoma
• Intervention / Treatment: Other: Collection of human biofluids; Other: Patient reported outcome measures

Detailed Description

The IMPRINT-study is a prospective biomarker study assessing the impact of different treatment field sizes and associated radiation doses on the patient's microbiome and metabolome, whereby the link with radiation-induced GI toxicities will be emphasized. Blood, urine and fecal samples will be longitudinally collected at 4 different time points: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT. To our knowledge, this is the first clinical research project relating the impact of multiple radiation parameters on fecal-, urine- and blood-based biomarkers to risk of GI toxicities in a homogeneously defined study population.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically proven (initial) adenocarcinoma of the prostate
• Localized (confined to primary site) and/or regional (spread to regional pelvic lymph nodes) disease stage at diagnosis
• Age ≥ 18 years
• RT is an integral part of the treatment - primary, adjuvant or salvage
• WHO performance status 0-2
• Administration of androgen deprivation therapy (ADT) before RT
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Signed informed consent form (ICF) according to ICH/GCP and national/regional regulations

Exclusion Criteria:

• Other primary tumor (except for non-melanoma skin cancer) diagnosed < 5 years before enrollment
• Diagnosis of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis)
• Administration of systemic therapy during RT other that ADT
• Subjected to antibiotic treatment or medically imposed dietary restrictions < 1 month prior to enrollment
• Body mass index (BMI) > 35
• Administration of pelvic RT < 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prostate (Bed) only RadioTherapy (PBRT); Primary, adjuvant or salvage RT of the prostate (bed) without RT of the pelvic nodal regions in the small pelvis, according to local hospital guidelines and protocols.	Other: Collection of human biofluids; Feces, blood and urine: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT; Other: Patient reported outcome measures; EORTC QLQ-C30, PR25: (1) shortly before and (2) shortly after RT treatment, as well as (3) one-month post-RT
Active Comparator: Whole Pelvis RadioTherapy (WPRT); Primary, adjuvant or salvage RT of the pelvic nodal regions in the small pelvis with possible additional RT of the prostate (bed), according to local hospital guidelines and protocols.	Other: Collection of human biofluids; Feces, blood and urine: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT; Other: Patient reported outcome measures; EORTC QLQ-C30, PR25: (1) shortly before and (2) shortly after RT treatment, as well as (3) one-month post-RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome profiles as assessed by fecal samples	Characterization of dynamic changes in the intestinal microbiota composition using 16S rRNA sequencing technology	Up to 3.5 months after inclusion
Metabolome profiles as assessed by fecal, blood and urine samples	Characterization of dynamic changes in the concentration of all small molecules (metabolites) in feces, blood and urine using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS)	Up to 3.5 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discovery of potential predictive biomarkers for the development of RT-induced GI toxicities	The identified microbiota and metabolite signatures will be investigated for association with incidence and severity of GI toxicities	Up to 3.5 months after inclusion
Incidence of GI and Genitourinary (GU) toxicities	GI and GU toxicities as per Common Terminology for Adverse Events (CTCAE) v4.0	Up to 3.5 months after inclusion
Patient reported QOL as per EORTC-QLQ C30	Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients	Up to 3.5 months after inclusion
Patient reported QOL as per EORTC-QLQ PR25	Validated questionnaire assessing the health-related QOL of prostate cancer patients	Up to 3.5 months after inclusion
Concentration of BEVs in fecal and blood samples	BEVs in fecal and blood samples will be separated and analyzed through the orthogonal implementation of ultrafiltration, size-exclusion chromatography (SEC) and density-gradient centrifugation, followed by biochemical characterization	Up to 3.5 months after inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Piet Ost, MD, PhD, University Ghent

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): August 8, 2022
• Study Completion (Actual): August 8, 2022

Study Registration Dates

• First Submitted: October 30, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; Radiotherapy; Metabolome
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: BC-07902

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No