Clinical trial NCT02853097: Cell-Free DNA and RNA in Blood fromMetastatic Prostate Cancer Patients
Official title: Studies of Cell-Free DNA and RNA in Blood From Patients Being Treated for Prostate Cancer
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Hormone-Resistant Prostate Cancer
Metastatic Prostate Carcinoma
Prostate Adenocarcinoma
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-08-02
Enrollment: 7
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Prostate cancer patients at various points throughout androgen deprivation therapy and at the initiation of androgen deprivation therapy, enzalutamide, abiraterone and docetaxel with either computed tomography measurable or evaluable disease or arising prostate specific antigen disease

Brief summary: This research trial studies cell-free deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in blood from patients with prostate cancer that does not respond to hormone therapy and has spread to other places in the body. Studying samples of blood from patients with prostate cancer may help doctors to learn more about the changes that occur in tumor cells over time and how they become resistant to anti-cancer drugs.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in AR-V7 presence
timeFrame: Baseline to 3 years
measure: Expression level of AR-V7 in serum cfRNA assessed by quantitative RT-PCR
timeFrame: Up to 3 years
measure: Time to start of another treatment
timeFrame: Time from start of treatment until the time that the patient begins another therapy, assessed up to 3 years
Secondary outcomes:
measure: Expression levels of AR-Vs (other than AR-V7) in serum cfRNA assessed by quantitative RT-PCR
timeFrame: Up to 3 years
measure: Tumor response as measured by Prostate Cancer Working Group
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: Keck Medical Center of USC Pasadena
state: California
Study officials:
affiliation: University of Southern California
name: Jacek Pinski, MD
role: PRINCIPAL_INVESTIGATOR
References: