Back to resultsInvestigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer. (PYRUS)
Primary Purpose
Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, Efficacy,, Safety and Tolerability,
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Intermittent dosing of AZD5363
Intermittent dosing of AZD5363
Intermittent dosing of AZD5363
Sponsored by
About this trial
This is an interventional screening trial for Metastatic Castrate-Resistant Prostate Cancer (mCRPC), focused on measuring Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, adenocarcinoma of the prostate,, prostate cancer,, progressive disease,, advanced disease.
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part A Group 1 Intermittent
Part A Group 2 Intermittent
Part B
Arm Description
Recruitment suspended and will not be re-opened. See intervention description below.
Recruitment complete. See intervention description below.
This part of the study will not be conducted following a review of data from Part A. See intervention description below.
Outcomes
Primary Outcome Measures
Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
Secondary Outcome Measures
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
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
Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker
Parts A and B: Progression-free survival (PFS)
Parts A and B: Quality of life (QoL)
EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01692262
Brief Title
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
Acronym
PYRUS
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
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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.
7. Study Design
Primary Purpose
Screening
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A Group 1 Intermittent
Arm Type
Experimental
Arm Description
Recruitment suspended and will not be re-opened. See intervention description below.
Arm Title
Part A Group 2 Intermittent
Arm Type
Experimental
Arm Description
Recruitment complete. See intervention description below.
Arm Title
Part B
Arm Type
Experimental
Arm Description
This part of the study will not be conducted following a review of data from Part A. See intervention description below.
Intervention Type
Drug
Intervention Name(s)
Intermittent dosing of AZD5363
Intervention Description
Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Recruitment suspended and will not be re-opened.
Intervention Type
Drug
Intervention Name(s)
Intermittent dosing of AZD5363
Intervention Description
Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue to study withdrawal. Recruitment complete.
Intervention Type
Drug
Intervention Name(s)
Intermittent dosing of AZD5363
Intervention Description
Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue until study drug withdrawal. This part of the study will not be conducted.
Primary Outcome Measure Information:
Title
Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
Time Frame
PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks
Title
Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
Time Frame
CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks
Title
Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
Time Frame
Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent
Title
Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
Time Frame
Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.
Secondary Outcome Measure Information:
Title
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
Time Frame
Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.
Title
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
Time Frame
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
Title
Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker
Time Frame
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
Title
Parts A and B: Progression-free survival (PFS)
Time Frame
Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.
Title
Parts A and B: Quality of life (QoL)
Description
EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires
Time Frame
QOL will be documented from date of randomization and for 12 weeks.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Stockman, MBCHB, PHD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Sarasota
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Research Site
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Cardiff, Wales
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
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