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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01692262
First received: September 19, 2012
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Castrate-Resistant Prostate Cancer (mCRPC),
Efficacy,
Safety and Tolerability,
Pharmacokinetics,
Pharmacodynamics,
Tumour Response.
Drug: Intermittent dosing of AZD5363
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
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)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ]

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 [ 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


Enrollment: 59
Study Start Date: November 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A Group 1 Intermittent
Recruitment suspended and will not be re-opened. See intervention description below.
Drug: Intermittent dosing of AZD5363
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.
Experimental: Part A Group 2 Intermittent
Recruitment complete. See intervention description below.
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. Recruitment complete.
Experimental: Part B
This part of the study will not be conducted following a review of data from Part A. See intervention description below.
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. This part of the study will not be conducted.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01692262

Locations
United States, Florida
Research Site
Sarasota, Florida, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, Michigan
Research Site
Ann Arbor, Michigan, United States
United States, New Jersey
Research Site
Hackensack, New Jersey, United States
United States, Tennessee
Research Site
Nashville, Tennessee, United States
United Kingdom
Research Site
Cardiff, Wales, United Kingdom
Research Site
London, United Kingdom
Research Site
Southampton, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Paul Stockman, MBCHB, PHD AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01692262     History of Changes
Other Study ID Numbers: D3610C00003, GU86
Study First Received: September 19, 2012
Last Updated: June 18, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Metastatic Castrate-Resistant Prostate Cancer (mCRPC),
adenocarcinoma of the prostate,
prostate cancer,
progressive disease,
advanced disease.

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 21, 2014