Clinical trial NCT02125617: Urokinase Plasminogen Activator Receptor in Abiraterone Treated Patients With Castration Resistant Prostate Cancer
Official title: uPAR in Blood From Zytiga® (Abiraterone) Treated Patients With Castration Resistant Prostate Cancer - a Predictive Marker of Response?
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Prostatic Neoplasms
Keywords: Castration-resistant prostate cancer
Abiraterone
Biomarker
Urokinase Plasminogen Activator Receptor
Plasma
Predictive markers
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2014-04-29
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients eligible for this study include patients with CRPC in progression after therapy with a taxane who are candidates for therapy with standard second line therapy abiraterone.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Impact of baseline uPAR cleavage products on response.
timeFrame: 6 months
Secondary outcomes:
measure: Impact of baseline plasma concentration of uPAR cleavage products on overall survival (OS).
timeFrame: 6 months
measure: Impact of baseline plasma concentration of uPAR cleavage products on progression free survival (PFS).
timeFrame: 6 months
measure: Impact of baseline plasma concentration of uPAR cleavage products on pain relief rate.
timeFrame: 6 months
measure: Impact of baseline plasma concentration of uPAR cleavage products on disease control rate (DCR).
timeFrame: 6 months
measure: Impact of baseline plasma concentration of uPAR cleavage products on serious adverse events (SAE).
timeFrame: 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University Hospital of Copenhagen, Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Kristoffer S Rohrberg, MD, Phd
role: STUDY_CHAIR
References: