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

Prostate Adenocarcinoma Clinical Trial

Official title:

Studies of Cell-Free DNA and RNA in Blood From Patients Being Treated for Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02853097
• Other study ID #: 4P-15-4
• Secondary ID: NCI-2016-009584P
• Status: Terminated
• Start date: June 14, 2016
• Est. completion date: September 27, 2020

Study information

• Verified date: April 2021
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: September 27, 2020
• Est. primary completion date: September 27, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hormone-Resistant Prostate Cancer
• Metastatic Prostate Carcinoma
• Prostate Adenocarcinoma
• Prostatic Neoplasms

Intervention

Other:
• Cytology Specimen Collection Procedure
Undergo blood collection
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Keck Medical Center of USC Pasadena	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in AR-V7 presence	Each of the 4 longitudinal cohorts will be analyzed separately (at least initially). Kaplan-Meier-like curves (likely adjusted for interval censoring) will be used to display the development of AR-V7 positivity. To complement the analysis of Cohort A, an exact logistic regression analysis will be used with the data from Cohort X with AR-V7 splice variant positivity as the dependent variable and time since start of ADT as the independent variable. Logistic regression will be used to assess the association between AR-V7 status at start of treatment and overall response to treatment.	Baseline to 3 years
Primary	Expression level of AR-V7 in serum cfRNA assessed by quantitative RT-PCR	Detectable AR-V7 will be associated with a shortened duration of treatment benefit (ADT, abiraterone, enzalutamide, docetaxel). Each of the 4 longitudinal cohorts will be analyzed separately (at least initially). A regression analysis based on the Cox proportional hazards model (if proportional hazards holds) will be used to assess the association between AR-V7 and time to new treatment. Initially, only the baseline AR-V7 status will be used. Next, AR-V7 will be included as a time dependent covariate; the model used may be modified to accommodate competing risks (if too many switch treatment p	Up to 3 years
Primary	Time to start of another treatment		Time from start of treatment until the time that the patient begins another therapy, assessed up to 3 years
Secondary	Expression levels of AR-Vs (other than AR-V7) in serum cfRNA assessed by quantitative RT-PCR		Up to 3 years
Secondary	Tumor response as measured by Prostate Cancer Working Group		Up to 3 years