Urokinase Plasminogen Activator Receptor in Abiraterone Treated Patients With Castration Resistant Prostate Cancer

Terminated

• Conditions: Prostatic Neoplasms
• Interventions: Drug: Abiraterone; Drug: Prednisolone

• Registration Number: NCT02125617
• Lead Sponsor: Kristoffer Staal Rohrberg

Brief Summary

The purpose of this study is to investigate cleavage products of the urokinase plasminogenactivator receptor (uPAR) in plasma from patients with castration resistant prostate cancer as a predictive marker of response to abiraterone.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-04-25
• Study First Submitted QC: 2014-04-28
• Study First Posted: 2014-04-29
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-18
• Last Update Posted: 2015-11-20
• Primary Completion: 2016-07
• Study Completion: 2017-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 3

Inclusion Criteria

• Signed informed consent.

• Age ≥18 years and male

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology

• Received at least one but not more than two cytotoxic chemotherapy regimens for metastatic CRPC. At least one regimen must have contained a taxane such as docetaxel.

• Prostate cancer progression as assessed by the investigator with one of the following:

  • PSA progression according to Prostate Cancer Working Group 2 (PCWG2) criteria
  • Solid Tumors (RECIST) criteria or bone scans with or without PSA progression.
  • Radiographic progression in soft tissue according to Response Evaluation Criteria in

• Ongoing androgen deprivation with serum testosterone <2.0 nM

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

• Platelet count ≥100,000/μL

• Serum albumin ≥30 g/dL

• Serum creatinine <1.5 x upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min

• Serum potassium ≥3.5 mmol/L

Exclusion Criteria

• Received abiraterone or MDV3100 in the past.

• Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection.

• Abnormal liver functions consisting of any of the following:

  • Serum bilirubin ≥1.5 x ULN (except for subjects with documented Gilbert's disease, for whom the upper limit of serum bilirubin is 51 µmol/l)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg); subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.

• Active or symptomatic viral hepatitis or chronic liver disease

• History of pituitary or adrenal dysfunction

• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or left ventricular ejection fraction (LVEF) of <50% at baseline.

• Known brain metastasis

• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study drug

• Any acute toxicities due to prior chemotherapy or radiotherapy that have not resolved to a NCI-CTCAE (Version 4.0) Grade of ≤1. Chemotherapy induced alopecia and Grade 2 peripheral neuropathy is allowed.

• Use of other anticancer therapy including cytotoxic, radionucleotide, and immunotherapy; diethylstilbestrol; PC-SPES; spironolactone (ie, ALDACTONE, SPIRONOL); and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer, within 4 weeks of Cycle 1 Day 1

• Prior systemic treatment with an azole drug (eg, fluconazole, itraconazole, ketoconazole) within 4 weeks of Cycle 1 Day 1

• Current enrolment in an investigational drug or device study or participation in such a study within 30 days of Day 1

• Condition or situation which, in the investigator's opinion, may put the subjects at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Castration-resistant prostate cancer, Progression after taxane	Abiraterone	Treated with abiraterone 1000 mg/day Prednisolone 10 mg/day
Castration-resistant prostate cancer, Progression after taxane	Prednisolone	Treated with abiraterone 1000 mg/day Prednisolone 10 mg/day

Primary Outcome Measures

Name	Time	Method
Impact of baseline uPAR cleavage products on response.	6 months	Impact of baseline plasma concentration of uPAR cleavage products on overall response rate (ORR) defined as the proportion of patients with radiologic response according to the RECIST criteria or PSA-response.

Secondary Outcome Measures

Name	Time	Method
Impact of baseline plasma concentration of uPAR cleavage products on pain relief rate.	6 months	Impact of baseline plasma concentration of uPAR cleavage products on pain relief rate.
Impact of baseline plasma concentration of uPAR cleavage products on serious adverse events (SAE).	6 months	Impact of baseline plasma concentration of uPAR cleavage products on serious adverse events (SAE).
Impact of baseline plasma concentration of uPAR cleavage products on overall survival (OS).	6 months	Impact of baseline plasma concentration of uPAR cleavage products on overall survival (OS).
Impact of baseline plasma concentration of uPAR cleavage products on progression free survival (PFS).	6 months	Impact of baseline plasma concentration of uPAR cleavage products on progression free survival (PFS).
Impact of baseline plasma concentration of uPAR cleavage products on disease control rate (DCR).	6 months	Impact of baseline plasma concentration of uPAR cleavage products on disease control rate (DCR).

Trial Locations

Locations (1)

University Hospital of Copenhagen, Rigshospitalet; 🇩🇰 Copenhagen, Denmark