Intestinal Akkermansia Muciniphila in Prostate Cancer (AkkPRO)

Impact of Intestinal Enrichment in Akkermansia Muciniphila by Next-generation Hormonal Therapies on Castration Resistant-prostate Cancer Response

Prostate cancer has the highest incidence and is the second leading cause of cancer death in men in western countries. Androgen deprivation therapy is the backbone treatment. However, after a latency hormone sensitive prostate cancer (HSPC) usually progresses to castration-resistant prostate cancer (CRPC) requiring treatments including next generation hormonal therapies with Abiraterone Acetate (AA). This, with limited survival.

A particularly challenging area of interest to improve outcome in cancer is the interaction between the microbiome and anti-cancer therapies. Emerging data demontrate in pre-clincal studies that prostate cancer alters the microbiota, with loss of diversity and depletion of beneficial bacteria including A. muciniphila. In the other hand, Androgen deprivation therapy, reverses these effects. Specifically, in advanced disease with castration-resistant prostate cancer (CRPC), it has been shown in small studies that Abiraterone Acetate, can modulate patient-associated gastro-intestinal microbiota through promoting the growth of A. muciniphila.

The goal of our study is to confirm that AA could promote fecal Akkermansia muciniphila growth and to use the enrichment of fecal Akkermansia muciniphila as a minimally invasive biomarker of response to AA in first line metastatic CRPC.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Diagnostic test: Biological samples

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, Pr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Safae Terrisse, Dr; Phone Number: +33142499783; Email: safae.terrisse@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic CRPC receiving next generation hormonal therapy

Description

Inclusion Criteria:

• Be willing and not opposed to the study
• Be ≥ 18 years of age at the time of inclusion.
• Histologically or cytologically documented adenocarcinoma of the prostate.
• Have metastatic castration-resistant prostate cancer with castrate-level testosterone (<50 ng/dL) during the study
• Initiation of abiraterone acetate therapy or any other next-generation hormonal therapies within 15 days after inclusion
• Participants must be able and willing to comply with the study visit schedule and study procedures
• Affiliated with French social security

Exclusion Criteria:

• CRPC patients who were previously treated with any next generation hormonal therapies in a metastatic CRPC setting
• Person under legal protection
• Inability to obtain the non-opposition

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Metastatic castration resistant prostate cancer (CRPC) receiving next generation hormonal therapy	Diagnostic test: Biological samples; Plasma sampling ans stool sampling; at inclusion; at 1 month; at 3 months; at progression within the 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative abundance of Akkermansia muciniphila	Between baseline and Month 1 of next-generation hormonotherapy (NGHT), compared between responders versus non-responders. The response is defined as an early PSA decrease > 50% at one month of NGHT.	At 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative variation of the relative abundance of Akkermansia muciniphila	Between baseline and Month 3 of AA treatment, compared between responders versus non responders	At 3 months
Relative variation in PSA	Relative variation in PSA between baseline PSA and nadir value, according to fecal Akkermansia muciniphila enrichment	At 1 month
Receiver Operating curve (ROC)	Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response	At 1 month
Receiver Operating curve (ROC)	Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response	At 3 months
PSA progression-free (PSA-PFS) survival	According to fecal Akkermansia muciniphila baseline relative abundance. PSA-PFS will be defined as the time from treatment initiation to PSA progression as per PCWG3 (The Prostate Cancer Working Group 3) or death, whichever occurs first; patients without event at M3 will be treated as censored observations.	At 3 months
Anti- Akkermansia muciniphila IgG levels		At baseline
Anti- Akkermansia muciniphila IgG levels		At 1 month
Anti- Akkermansia muciniphila IgG levels		At 3 months
Anti- Akkermansia muciniphila IgA levels		At baseline
Anti- Akkermansia muciniphila IgA levels		At 1 month
Anti- Akkermansia muciniphila IgA levels		At 3 months
Alpha diversity	Assessed by Shannon index (Microbial Richness)	At baseline
Alpha diversity	Assessed by Shannon index (Microbial Richness)	At 1 month
Alpha diversity	Assessed by Shannon index (Microbial Richness)	At 3 months
Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At baseline
Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At 1 month
Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2024
• Primary Completion (Estimated): September 15, 2025
• Study Completion (Estimated): November 15, 2025

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Estimated): February 5, 2024

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: APHP221176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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