Biomarkers of Androgen Response and Resistance In Evolution During a Rising PSA

NCT02429193 | Completed Phase 2 DMC

• 1 other identifier: BARRIER-P
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  18 months

Secondary Outcomes (2)

• Rate of PSA increase

  18 months

• Time to PSA progression

  18 months

Other Outcomes (1)

• Number of participants with adverse events from the administration of abiraterone, enzalutamide, and prednisone to men with early stage prostate cancer.

  18 months

Study Arms (1)

Abiraterone / enzalutamide

EXPERIMENTAL

Abiraterone + prednisone; Enzalutamide

Drug: Abiraterone + prednisone; Drug: Enzalutamide

Interventions

Abiraterone + prednisone DRUG

Abiraterone acetate (1000 mg/day p.o.) + prednisone (5 mg b.i.d., p.o.)

Also known as: abiraterone acetate, Zytiga, prednisone

Abiraterone / enzalutamide

Enzalutamide DRUG

Enzalutamide (160 mg/day p.o.)

Also known as: Xtandi

Abiraterone / enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

British Columbia Cancer Agency, Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Interventions

abiraterone; Prednisone; Abiraterone Acetate; enzalutamide

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstenes; Androstanes

Study Officials

• Anthony Joshua, MD,MBBS,PhD,FRACP

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 29, 2015
• Study Start: March 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01

Locations

CA (2)