Metastatic Castration-resistant Prostate Cancer
Conditions
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.
Interventions
DIAGNOSTIC_TESTBiological samples
Plasma sampling ans stool sampling * at inclusion * at 1 month * at 3 months * at progression within the 3 months
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 1 month | Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response |
| 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. |
| Anti- Akkermansia muciniphila IgG levels | At baseline | — |
| Anti- Akkermansia muciniphila IgA levels | At baseline | — |
| Alpha diversity | At baseline | Assessed by Shannon index (Microbial Richness) |
| Beta diversity | At baseline | Assessed by Bray-Curtis dissimilarity (Microbial Diversity) |
Countries
France
Contacts
CONTACTSafae Terrisse, Dr
CONTACTJérôme Lambert, Pr
Outcome results
None listed