Biomarkers of Androgen Response and Resistance In Evolution During a Rising PSA (BARRIER-P)
Primary Purpose
Castration-resistant Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Abiraterone + prednisone
Enzalutamide
Sponsored by
About this trial
This is an interventional treatment trial for Castration-resistant Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically or cytologically confirmed prostate cancer
- Able to read and understand the consent form, either alone or with the aid of a translator
- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nmol/L). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patients who have not undergone orchiectomy), they must remain on continuous androgen suppression therapy throughout the study
- Patients receiving bone-targeted therapies must be on stable doses for at least 4 weeks prior to enrollment
- Historical frozen/paraffin-embedded diagnostic tissue specimens are available for analysis (i.e. radical prostatectomy or biopsy tissue)
- Documented metastatic disease by positive bone scan or metastatic lesions (on CT or MRI) that can be biopsied with an anticipated minimum of 4 cores, as assessed by the local radiologist
- prostate cancer progression at study entry defined as one or more of the following criteria: i. Rising PSA: minimum of two rising PSA levels with an interval of ≥ 1 week between each determination ii. Soft tissue disease progression, as defined by RECIST 1.1 iii. Bone disease progression, as defined by PCWG2 with two or more new lesions on bone scan
- PSA value at screening visit ≥ 2 µg/L (2 ng/mL)
- ECOG performance status 0-2
Adequate organ and BM function, as defined by the following criteria:
i. absolute neutrophil count ≥1,500/µL ii. platelets ≥100,000/µL iii. total bilirubin ≤1.5 × institutional upper limit of normal (ULN) iv. AST(SGOT) or ALT(SGPT) ≤2.5 × institutional ULN v. creatinine ≤1.5 × institutional ULN or below
- Serum albumin ≥ 3.0 g/dL
- Serum potassium ≥ 3.5 mmol/L
- Haemoglobin ≥ 10.0 g/dL, independent of transfusion
- Asymptomatic or mildly symptomatic from prostate cancer
- Life expectancy of > 6 months
- Able to swallow study drugs
- Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration
Exclusion Criteria:
- Patients with known hypersensitivity or allergy to abiraterone acetate, enzalutamide or any of their excipients.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (NYHA Class 3 or greater), cirrhosis with a Child-Pugh level of B or greater or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months, hypotension (defined by systolic blood pressure < 86 mmHg at Screening visit), hypertension (defined by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening visit), bradycardia (defined by < 50 beats per minute on ECG performed at screening), active peptic ulcer disease, clinically significant gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis), any seizure disorder or psychiatric illness, and social situations that would limit compliance with study requirements
- Active invasive malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
- Known or suspected brain metastasis or leptomeningeal disease
- Radiotherapy within the past 4 weeks, except for low dose palliative radiation to bone of ≤5 fractions
- Treatment with 5-α reductase inhibitors (finasteride, dutasteride), androgen receptor antagonists (bicalutamide, nilutamide, flutamide), estrogens, cyproterone within 4 weeks of Day 1 visit
Sites / Locations
- British Columbia Cancer Agency, Vancouver Cancer Centre
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Abiraterone / enzalutamide
Arm Description
Abiraterone + prednisone; Enzalutamide
Outcomes
Primary Outcome Measures
Change in expression of androgen receptor abnormalities (e.g. ARV7, AR mutations) following abiraterone/enzalutamide treatment
The change in protein expression of androgen receptor (AR7) splice variant and AR / AR pathway mutations as a mechanism of resistance to abiraterone/enzalutamide is evaluated by measuring the difference in a quantitative immunohistochemical biomarker between assays performed before and after treatment.
Secondary Outcome Measures
Rate of PSA increase
Time to PSA progression
PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 µg/L (2 ng/mL) above the nadir.
Full Information
NCT ID
NCT02429193
First Posted
March 25, 2015
Last Updated
January 10, 2020
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT02429193
Brief Title
Biomarkers of Androgen Response and Resistance In Evolution During a Rising PSA
Acronym
BARRIER-P
Official Title
An Open-label Phase 2 Multi-center Study of Enzalutamide and Abiraterone and Biomarkers of Androgen Response and Resistance During Rising PSA: BARRIER-P Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
September 1, 2019 (Actual)
Study Completion Date
September 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label phase 2 multi-center study of abiraterone and enzalutamide in men with castration-resistant prostate cancer. Sixteen patients will be enrolled over 18 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-resistant Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Abiraterone / enzalutamide
Arm Type
Experimental
Arm Description
Abiraterone + prednisone; Enzalutamide
Intervention Type
Drug
Intervention Name(s)
Abiraterone + prednisone
Other Intervention Name(s)
abiraterone acetate, Zytiga, prednisone
Intervention Description
Abiraterone acetate (1000 mg/day p.o.) + prednisone (5 mg b.i.d., p.o.)
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi
Intervention Description
Enzalutamide (160 mg/day p.o.)
Primary Outcome Measure Information:
Title
Change in expression of androgen receptor abnormalities (e.g. ARV7, AR mutations) following abiraterone/enzalutamide treatment
Description
The change in protein expression of androgen receptor (AR7) splice variant and AR / AR pathway mutations as a mechanism of resistance to abiraterone/enzalutamide is evaluated by measuring the difference in a quantitative immunohistochemical biomarker between assays performed before and after treatment.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Rate of PSA increase
Time Frame
18 months
Title
Time to PSA progression
Description
PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 µg/L (2 ng/mL) above the nadir.
Time Frame
18 months
Other Pre-specified Outcome Measures:
Title
Number of participants with adverse events from the administration of abiraterone, enzalutamide, and prednisone to men with early stage prostate cancer.
Description
The number of participants experiencing adverse events will be evaluated to determine the safety of abiraterone, enzalutamide, and prednisone treatment in men with early stage prostate cancer, .
Time Frame
18 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with histologically or cytologically confirmed prostate cancer
Able to read and understand the consent form, either alone or with the aid of a translator
Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nmol/L). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patients who have not undergone orchiectomy), they must remain on continuous androgen suppression therapy throughout the study
Patients receiving bone-targeted therapies must be on stable doses for at least 4 weeks prior to enrollment
Historical frozen/paraffin-embedded diagnostic tissue specimens are available for analysis (i.e. radical prostatectomy or biopsy tissue)
Documented metastatic disease by positive bone scan or metastatic lesions (on CT or MRI) that can be biopsied with an anticipated minimum of 4 cores, as assessed by the local radiologist
prostate cancer progression at study entry defined as one or more of the following criteria: i. Rising PSA: minimum of two rising PSA levels with an interval of ≥ 1 week between each determination ii. Soft tissue disease progression, as defined by RECIST 1.1 iii. Bone disease progression, as defined by PCWG2 with two or more new lesions on bone scan
PSA value at screening visit ≥ 2 µg/L (2 ng/mL)
ECOG performance status 0-2
Adequate organ and BM function, as defined by the following criteria:
i. absolute neutrophil count ≥1,500/µL ii. platelets ≥100,000/µL iii. total bilirubin ≤1.5 × institutional upper limit of normal (ULN) iv. AST(SGOT) or ALT(SGPT) ≤2.5 × institutional ULN v. creatinine ≤1.5 × institutional ULN or below
Serum albumin ≥ 3.0 g/dL
Serum potassium ≥ 3.5 mmol/L
Haemoglobin ≥ 10.0 g/dL, independent of transfusion
Asymptomatic or mildly symptomatic from prostate cancer
Life expectancy of > 6 months
Able to swallow study drugs
Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration
Exclusion Criteria:
Patients with known hypersensitivity or allergy to abiraterone acetate, enzalutamide or any of their excipients.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (NYHA Class 3 or greater), cirrhosis with a Child-Pugh level of B or greater or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months, hypotension (defined by systolic blood pressure < 86 mmHg at Screening visit), hypertension (defined by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening visit), bradycardia (defined by < 50 beats per minute on ECG performed at screening), active peptic ulcer disease, clinically significant gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis), any seizure disorder or psychiatric illness, and social situations that would limit compliance with study requirements
Active invasive malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
Known or suspected brain metastasis or leptomeningeal disease
Radiotherapy within the past 4 weeks, except for low dose palliative radiation to bone of ≤5 fractions
Treatment with 5-α reductase inhibitors (finasteride, dutasteride), androgen receptor antagonists (bicalutamide, nilutamide, flutamide), estrogens, cyproterone within 4 weeks of Day 1 visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Joshua, MD,MBBS,PhD,FRACP
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
British Columbia Cancer Agency, Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Biomarkers of Androgen Response and Resistance In Evolution During a Rising PSA
We'll reach out to this number within 24 hrs