Intestinal Akkermansia Muciniphila in Prostate Cancer

Metastatic Castration-resistant Prostate Cancer Clinical Trial

— AkkPRO  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06242509
• Other study ID #: APHP221176
• Status: Not yet recruiting
• Start date: February 15, 2024
• Est. completion date: November 15, 2025

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Safae Terrisse, Dr
• Phone: +33142499783
• Email: safae.terrisse[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 52
• Est. completion date: November 15, 2025
• Est. primary completion date: September 15, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Diagnostic Test:
• Biological samples
Plasma sampling ans stool sampling at inclusion at 1 month at 3 months at progression within the 3 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Relative variation in PSA	Relative variation in PSA between baseline PSA and nadir value, according to fecal Akkermansia muciniphila enrichment	At 1 month
Secondary	Receiver Operating curve (ROC)	Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response	At 1 month
Secondary	Receiver Operating curve (ROC)	Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response	At 3 months
Secondary	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
Secondary	Anti- Akkermansia muciniphila IgG levels		At baseline
Secondary	Anti- Akkermansia muciniphila IgG levels		At 1 month
Secondary	Anti- Akkermansia muciniphila IgG levels		At 3 months
Secondary	Anti- Akkermansia muciniphila IgA levels		At baseline
Secondary	Anti- Akkermansia muciniphila IgA levels		At 1 month
Secondary	Anti- Akkermansia muciniphila IgA levels		At 3 months
Secondary	Alpha diversity	Assessed by Shannon index (Microbial Richness)	At baseline
Secondary	Alpha diversity	Assessed by Shannon index (Microbial Richness)	At 1 month
Secondary	Alpha diversity	Assessed by Shannon index (Microbial Richness)	At 3 months
Secondary	Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At baseline
Secondary	Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At 1 month
Secondary	Beta diversity	Assessed by Bray-Curtis dissimilarity (Microbial Diversity)	At 3 months