A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD3514 in Patients With Metastatic Castration-Resistant Prostate Cancer.

AstraZeneca1 site in 1 country64 target enrollmentAugust 2010

ConditionsProstate Cancer

InterventionsAZD3514

DrugsAZD3514

Overview

Phase: Phase 1
Intervention: AZD3514
Conditions: Prostate Cancer
Sponsor: AstraZeneca
Enrollment: 64
Locations: 1
Primary Endpoint: To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC.
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The main purpose of the study is to investigate the safety and tolerability of AZD3514 when given orally to patients with castration-resistant prostate cancer (CRPC)

Registry

clinicaltrials.gov

Start Date

August 2010

End Date

October 2015

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Males aged 20 years or older.
•Histologically or Cytologically proven diagnosis of prostate cancer for which no standard therapy is currently considered appropriate.
•Documented evidence of metastatic prostate cancer
•Presence of progressive disease defined as one or more:
•Biochemical progression of the prostate cancer
•Progression as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 guidelines
•Two or more new metastatic bone lesions from bone scans from a previous assessment
•Serum testosterone concentration less or equals 50 ng/dL
•World Health Organization (WHO) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
•Sexually active males should be willing to use condoms

Exclusion Criteria

•Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAEv4) grade 1 except for alopecia or toxicities related to the use of gonadotropin-releasing hormone agonists
•Medically important spinal cord compression or brain metastases
•Medically important evidence of severe or uncontrolled systemic disease
•History of hypersensitivity to active or inactive excipients of AZD3514 or drugs with a similar chemical structure or class to AZD3514
•Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD3514
•Inadequate bone marrow reserve or organ function
•Any medically important factors identified from electrocardiogram (ECG) measurements
•Concurrent or recent treatment with certain medications or medical procedures
•The following criteria exclude patients from entering the AZD3514 administered in combination with abiraterone acetate cohort(s):
•As judged by the investigator, any evidence of severe or uncontrolled systemic diseases or conditions, including adrenocortical insufficiency or a history of cardiovascular disease including heart failure (currently there are no randomized data for the use of abiraterone acetate in patients with LVEF \< 50% or NYHA Class III or IV heart failure), which would make it undesirable for the patient to participate in the trial. See the full local prescribing information for abiraterone acetate for more detail

Arms & Interventions

A

Ascending doses of AZD3514 administered orally to patients to define the maximum tolerated dose (MTD)

Intervention: AZD3514

Outcomes

Primary Outcomes

To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC.

Time Frame: At every visit.

Secondary Outcomes

To investigate the effect of AZD3514 on biomarkers of AR expression in paired pre- and post-dose tumour biopsies.(July 2012 - Feb 2013)
To define the MTD, if possible, a lower biologically-effective dose(s) or maximum feasible dose (if decided by the Safety Review Committee (SRC) and AstraZeneca).(After each Cohort.)
To obtain a preliminary assessment of the anti-tumour activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate by evaluation of counts of Circulating Tumour Cells (CTCs).(Visits 1, 6, 8, 9, 10, follow-up visits, discontinuation visit)
To characterise the PK of AZD3514 after a single oral dose and at steady state after multiple oral doses.(After each Cohort.)
To obtain an assessment of the activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate on the circulating levels of prostate-specific antigen (PSA).(Visits 1, 10, follow-up visits, discontinuation visit)
To investigate safety, tolerability, MTD (and/or biologically-effective dose(s) or maximum feasible dose) and PK of AZD3514 and abiraterone when administered in combination, in patients who have not received prior treatment with abiraterone acetate(At every visit)
To compare the PK of AZD3514 monotherapy in patients who have been fed or fasted before the administration of study treatment(At visits 2 and 4)