Intestinal Akkermansia Muciniphila in Prostate Cancer

Not yet recruiting

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Metastatic castration resistant prostate cancer (CRPC) receiving next generation hormonal therapy	Biological samples	-

Primary Outcome Measures

Name	Time	Method
Relative abundance of Akkermansia muciniphila	At 1 month	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.

Secondary Outcome Measures

Name	Time	Method
Beta diversity	At 3 months	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)
Anti- Akkermansia muciniphila IgG levels	At 3 months
Alpha diversity	At 3 months	Assessed by Shannon index (Microbial Richness)
PSA progression-free (PSA-PFS) survival	At 3 months	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.
Relative variation in PSA	At 1 month	Relative variation in PSA between baseline PSA and nadir value, according to fecal Akkermansia muciniphila enrichment
Receiver Operating curve (ROC)	At 3 months	Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response
Anti- Akkermansia muciniphila IgA levels	At 3 months
Relative variation of the relative abundance of Akkermansia muciniphila	At 3 months	Between baseline and Month 3 of AA treatment, compared between responders versus non responders

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