Cell-Free DNA and RNA in Blood fromMetastatic Prostate Cancer Patients

PRIMARY OBJECTIVES:

I. To document the appearance of androgen receptor isoform splice variant 7 (AR-V7)
expression over the course of therapy in castration-resistant prostate cancer (CRPC).

II. To determine whether detectable AR-V7 is associated with a shortened duration of
treatment benefit of abiraterone or enzalutamide.

SECONDARY OBJECTIVES:

I. To determine how the presence and expression level of AR-V7 impacts response to docetaxel.

II. To determine at what point AR-V7 arises during androgen deprivation therapy (ADT) and how
its presence and expression corresponds to castration resistance.

TERTIARY OBJECTIVES:

I. To determine if androgen receptor isoform splice variants (AR-Vs) other than AR-V7 play a
role in resistance and / or response to the therapies explored in this study.

II. To determine if, in patients who do not express mutations in androgen receptor (AR),
other genetic alterations are associated with treatment outcomes to the therapies explored in
this study.

OUTLINE:

Patients undergo blood collection every 4-12 weeks during ADT, abiraterone and / or
enzalutamide and docetaxel. Patients switched from ADT to either abiraterone or enzalutamide
during the study will undergo phlebotomy every 6-12 weeks. Samples are analyzed for cell-free
ribonucleic acid (cfRNA), cell-free deoxyribonucleic acid (cfDNA), AR-V7, and other AR-Vs via
quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

After completion of study, patients are followed up for 3 years.

Inclusion Criteria:

- A diagnosis of histologically confirmed prostate adenocarcinoma and falling into one
of the following 5 groups:

- Currently receiving ADT (previously untreated for metastatic disease)

- These patients will be grouped into 3 cohorts: having received ADT for 3-6
months; for 1-2 years; and for > 3 years

- Scheduled to begin treatment with ADT (previously untreated for metastatic
disease)

- Scheduled to begin treatment with enzalutamide (castration resistant / has
received ADT / may have received abiraterone)

- Scheduled to begin treatment with abiraterone (castration resistant / has
received ADT / may have received enzalutamide)

- Scheduled to begin treatment with docetaxel (castration resistant / has received
ADT / has received enzalutamide and/or abiraterone)

- Have been diagnosed with either hormone-naive or castrate-resistant metastatic disease

- Ability and willingness to provide written and informed consent

Exclusion Criteria:

- Patients who receive combined ADT with docetaxel for hormone-naive metastatic prostate
cancer

- Patients on intermittent ADT