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Completed

NCT Number: NCT01692262

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

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.

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Key information

Conditions

Metastatic Castrate-Resistant Prostate Cancer (mCRPC), Disease Attributes Disease Progression Efficacy, Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Pharmacodynamics, Pharmacokinetics, Prostatic Diseases Prostatic Neoplasms Safety and Tolerability, Tumour Response. Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Cardiff, Wales, United Kingdom

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About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Intermittent dosing of AZD5363

Drug

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.

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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 outcomes

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Parts A and B: Quality of life (QoL)

    Time frame: QOL will be documented from date of randomization and for 12 weeks.

    EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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)

Acronym: PYRUS

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Sep 25, 2012
Registry last updated
Jun 19, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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