Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer. (PYRUS)

This study is currently recruiting participants.
Verified March 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01692262
First received: September 19, 2012
Last updated: March 19, 2014
Last verified: March 2014

September 19, 2012
March 19, 2014
October 2012
May 2014   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA) [ Time Frame: PSA measured from beasline for every 4 weeks. Primary assesment is at 12 weeks ] [ Designated as safety issue: No ]
  • Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC) [ Time Frame: CTC measured from beasline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01692262 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Parts A and B: Quality of life (QoL) [ Time Frame: QOL will be documented from date of randomization and for 12 weeks. ] [ Designated as safety issue: No ]
    EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires
  • 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. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Parts A and B: Quality of life (QoL): 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. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
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)

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.

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)

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
  • Metastatic Castrate-Resistant Prostate Cancer (mCRPC),
  • Efficacy,
  • Safety and Tolerability,
  • Pharmacokinetics,
  • Pharmacodynamics,
  • Tumour Response.
  • Drug: Intermittent dosing of AZD5363
    Recruitment to this group is currently temporarily suspended. Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off).
  • Drug: Intermittent dosing of AZD5363
    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.
  • Drug: Intermittent dosing of AZD5363
    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.
  • Experimental: Part A Group 1 Intermittent
    Temporarily Suspended. See intervention description below.
    Intervention: Drug: Intermittent dosing of AZD5363
  • Experimental: Part A Group 2 Intermittent
    See intervention description below.
    Intervention: Drug: Intermittent dosing of AZD5363
  • Experimental: Part B
    See intervention description below.
    Intervention: Drug: Intermittent dosing of AZD5363
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
66
February 2015
May 2014   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com
United States,   United Kingdom
 
NCT01692262
D3610C00003, GU86
Not Provided
AstraZeneca
AstraZeneca
Not Provided
Study Director: Paul Stockman, MBCHB, PHD AstraZeneca
AstraZeneca
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP