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

NCT ID: NCT02429193

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-09-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abiraterone / enzalutamide

Abiraterone + prednisone; Enzalutamide

Group Type: EXPERIMENTAL

Abiraterone + prednisone

Intervention Type: DRUG

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

Enzalutamide

Intervention Type: DRUG

Enzalutamide (160 mg/day p.o.)

Interventions

Abiraterone + prednisone

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

Intervention Type: DRUG

Enzalutamide

Enzalutamide (160 mg/day p.o.)

Intervention Type: DRUG

Other Intervention Names

abiraterone acetate; Zytiga; prednisone; Xtandi

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony Joshua, MD,MBBS,PhD,FRACP

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

British Columbia Cancer Agency, Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

BARRIER-P

Identifier Type: -

Identifier Source: org_study_id