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

Prostate Cancer Clinical Trial

— IMPRINT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04638049
• Other study ID #: BC-07902
• Status: Completed
• Phase: N/A
• Start date: August 25, 2020
• Est. completion date: August 8, 2022

Study information

• Verified date: October 2020
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 8, 2022
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Adenocarcinoma
• Prostate Cancer
• Prostatic Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
Belgium	Ghent University Hospital	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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