Clinical trial NCT01692262: Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
Official title: A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity,Safety,Tolerability,and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)(PYRUS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Castrate-Resistant Prostate Cancer (mCRPC),
Efficacy,
Safety and Tolerability,
Pharmacokinetics,
Pharmacodynamics,
Tumour Response.
Keywords: Metastatic Castrate-Resistant Prostate Cancer (mCRPC),
adenocarcinoma of the prostate,
prostate cancer,
progressive disease,
advanced disease.
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-09-25
Enrollment: 59
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy, in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated in patients who have progressed after chemotherapy (Part A) and in patients who have progressed before receiving chemotherapy (Part B).

Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off).

Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients on a dose and schedule selected from Part A.

Detailed description: A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety, Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) (PYRUS)

Eligibility criteria: Inclusion Criteria:

* Provision of informed consent
* Males aged 18 years and older
* Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features for which no standard therapy is currently considered appropriate
* Documented evidence of Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
* Part A: Patients must have received prior docetaxel-based chemotherapy for mCRPC and have a Circulating Tumour Cell score of 5;
* Part B: Patients must have progressed before receiving any chemotherapy for mCRPC;

Exclusion Criteria:

* Any prior exposure to agents which inhibit AKT as the primary pharmacological activity
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus
* Spinal cord compression or brain metastases unless asymptomatic, treated, and stable and not requiring steroids
* Clinically significant abnormalities of glucose metabolism
* Major surgery within the previous 4 weeks

Primary outcomes:
measure: Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
timeFrame: PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks
measure: Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
timeFrame: CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks
measure: Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
timeFrame: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent
measure: Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
timeFrame: Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.
Secondary outcomes:
measure: Parts A and B: Safety and tolerability of AZD5363 in terms of adverse events, serious adverse events (including death) and safety measures: ECG, ECHO/MUGA, physical examination, pulse, blood pressure, weight and laboratory variables
timeFrame: Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.
measure: Parts A and B: AZD5363 PK: time to maximum plasma concentration, terminal rate constant,terminal half life, area under plasma concentration time curve, plasma clearance & volume of distribution
timeFrame: Multiple AZD5363 PK blood sample assessments.AZD5363 plasma concentration blood samples will be taken on Day 1(pre-dose,2,4,8 hours post-dose);D2(pre-dose);D8(continous) or D11(intermittent) (pre-dose and at 2,4,and 8 hours post-dose);D15,Cyc
measure: Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker
timeFrame: Multiple PD blood sample assessments.PD blood samples will be taken on the same schedule as PK sample and then Day 1 of every 12 weeks thereafter, and at the discontinuation visit
measure: Parts A and B: Progression-free survival (PFS)
timeFrame: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.
measure: Parts A and B: Quality of life (QoL)
timeFrame: QOL will be documented from date of randomization and for 12 weeks.
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Cardiff, Wales
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Paul Stockman, MBCHB, PHD
role: STUDY_DIRECTOR
References: