Study to Determine the Feasibility, Evaluability and Variability in Markers of Drug Action in Castration Resistant Prostate Cancer — BIOMETHS  

Metastatic Castration Resistant Prostate Cancer Clinical Trial

Official title: BIOMETHS Study. A Methodology Study to Determine the Feasibility, Evaluability and Temporal Variability in Candidate Pharmacodynamic Markers of Drug Action in Castration Resistant Prostate Cancer

Status Completed

Clinical Trial Summary

This is a biopsy feasibility study in which patients with castration resistant prostate cancer (CRPC) will be asked to donate primary and metastatic tumour tissue (both archival and de novo), blood samples, a urine specimen and clinical data for research.

Clinical Trial Description

The study aims to determine the feasibility of sampling and evaluability of biomarkers in CRPC tissue samples and circulating tumour cells (CTCs). Exploratory biomarker analysis may include, but will not be limited to, understanding the potential proof of mechanism (POM), proof of principle (POP) or predictive biomarkers of response to potential therapeutic agents for CRPC patients, or factors that may influence the development of CRPC.

This study is predicated on the continued development of agents targeting the PI3K pathway such as AZD(AstraZeneca Drug)8186 (PI3Kb); AZD5363 (Akt) and AZD2014 (mTOR) and anti-hormonals which are expected to deliver benefit in the management of tumours dependent on PI3K signalling as a result of e.g. phosphatase and tensin homolog (PTEN) deficiency or androgen receptor activation.

Loss of PTEN is common in CRPC. Current data indicate that AZD8186 inhibits PI3K downstream signalling in PTEN deficient but not in PTEN proficient cells and hence POM and efficacy will need to be determined in tumours with PTEN protein loss. In future studies, paired biopsy tumour tissue will be accessible for assessment of POM and PTEN status, either bone metastases lymph node metastases, or within the prostate tumour.

Recruitment of patients will be carried out in two stages as follows:

Stage 1 The first 10 eligible and consenting patients will be enrolled in the study and will undergo sequential biopsies. For all stage one participants, the PTEN status will be retrospectively determined from archival tumour samples by immuno-histochemistry (IHC).

The results of the PTEN analysis from Stage 1, will determine the number of patients in Stage 2 that must be PTEN positive or PTEN null. For this study the intent is to have equal numbers of each type i.e. ten PTEN positive and ten PTEN null.

Stage 2

In Stage 2, patients will be asked to sign a pre-screening consent form for their archival tumour sample to be analysed for PTEN status prior to undergoing any main study screening procedures. If their PTEN status matches one of the available slots they will be enrolled into the study.

Once a cohort reaches ten PTEN positive and ten PTEN null patients, it will close to recruitment. ;

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

• NCT number: NCT02424448
• Study type: Observational
• Source: The Christie NHS Foundation Trust
• Status: Completed
• Phase: N/A
• Start date: December 2014
• Completion date: July 2016