An Open Label Prostate Cancer Study in Japanese Patients

Study Overview
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Brief Summary
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The primary aim of study is to gain an initial assessment of safety and tolerability of AZD3514 in Japanese patients together with assessing Pharmacokinetics (PK) and gaining a preliminary assessment of anti-tumour action. In this study, AZD3514 will be administered to Japanese patients with metastatic castration resistant prostate cancer.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: AZD3514


Participation Criteria
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Eligibility Criteria
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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 Serum testosterone concentration ≤50 ng/dL World Health Organisation (WHO) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks Exclusion Criteria: 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 Concurrent or recent treatment with certain medications or medical procedures Any medically important factors identified from electrocardiogram (ECG) measurements

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3514<br>Ascending doses of AZD3514 administered orally to patients to define the maximum tolerated dose (MTD) | Drug: AZD3514<br>* Patients will be given AZD3514 tablets or capsules administered orally as a single dose, and then multiple once-daily dosing following a 7 day washout.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of AZD3514 when given orally to Japanese patients with castration resistant prostate cancer | Number of participants with adverse events | All AEs will be collected throughout the study, from informed consent until 30 days after the end of study treatment. The total duration of this time frame can not be specified | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define the maximum tolerated dose, if possible, a lower biologically-effective dose(s) or maximum feasible dose of AZD3514 | A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation and considered to be related to AZD3514 therapy during the single dose period and the first 21 days of multiple dosing (ie, by study day 29) | during the single dose period and the first 21 days of multiple dosing (ie, by study day 29) | 
| To characterise the pharmacokinetics of AZD3514 after a single oral dose and at steady state after multiple oral doses | To characterise the pharmacokinetics of AZD3514 after a single oral dose and at steady state after multiple oral doses Cmax Cmax at steady state (Cmax, ss) time to maximum concentration (tmax) tmax at steady state (tmax, ss) terminal elimination rate constant (λz) (AUC(0-t)) total clearance and terminal phase (Vz) of AZD3514 | Multiple timepoints taken, begining at Day 1 and until 48 hrs after last dose. The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | 
| To obtain an preliminary assessment of the anti-tumour activity of AZD3514 |  | Every 12 weeks | 
| To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA) |  | Day 8, 15, 29 and every 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Metastatic, Castration resistant, Prostate cancer, Androgen receptor, Down regulation, Japanese