Metastatic Castrate-Resistant Prostate Cancer (mCRPC),Phase 1PYRUSNCT01692262
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
A Phase 1 study testing Intermittent dosing of AZD5363 in people with Metastatic Castrate-Resistant Prostate Cancer (mCRPC), and Efficacy,, run by AstraZeneca at 8 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, Efficacy,, Safety and Tolerability,
- What is being tested?
- Intermittent dosing of AZD5363
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Nov 2012to Jun 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
Research Site
Ann Arbor, Michigan
Research Site
Boston, Massachusetts
Research Site
Hackensack, New Jersey
Research Site
Nashville, Tennessee
Research Site
Sarasota, Florida
United Kingdom3 sites
Research Site
Cardiff, Wales
Research Site
London
Research Site
Southampton
About this study
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)
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.
Read the 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)
- Conditions
- Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, Efficacy,, Safety and Tolerability,, Pharmacokinetics,, Pharmacodynamics,, Tumour Response.
- Being tested
- Intermittent dosing of AZD5363
- Keywords
- Metastatic Castrate-Resistant Prostate Cancer (mCRPC),, adenocarcinoma of the prostate,, prostate cancer,, progressive disease,, advanced disease.
- Medical subject headings
- Prostatic Neoplasms, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent dosing of AZD5363Drug
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.
Intermittent dosing of AZD5363Drug
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.
Intermittent dosing of AZD5363Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A Group 1 Intermittent | Experimental | Recruitment suspended and will not be re-opened. See intervention description below. Receives: Drug: Intermittent dosing of AZD5363 |
| Part A Group 2 Intermittent | Experimental | Recruitment complete. See intervention description below. Receives: Drug: Intermittent dosing of AZD5363 |
| Part B | Experimental | This part of the study will not be conducted following a review of data from Part A. See intervention description below. Receives: Drug: Intermittent dosing of AZD5363 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)
Measured: PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks
Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)
Measured: CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks
Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate
Measured: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent
Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status
Measured: Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.
Secondary outcomes (5)
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
Measured: Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.
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
Measured: 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
Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker
Measured: 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
Parts A and B: Progression-free survival (PFS)
Measured: Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.
Parts A and B: Quality of life (QoL)
EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires
Measured: QOL will be documented from date of randomization and for 12 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study startNov 2012
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castrate-Resistant Prostate Cancer (mCRPC),Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Stockman, MBCHB, PHD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01692262
- Sponsor's protocol ID
- D3610C00003
- Other IDs
- GU86
- Acronym
- PYRUS
- Status last verified
- Jun 2014
- First submitted
- 19 Sep 2012
- Last updated
- 19 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01692262
- Acronym / sponsor ID
- PYRUS / D3610C00003
- 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.
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 25 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A Group 1 Intermittent | Experimental | Drug: Intermittent dosing of AZD5363Recruitment suspended and will not be re-opened. See intervention description below. |
| Part A Group 2 Intermittent | Experimental | Drug: Intermittent dosing of AZD5363Recruitment complete. See intervention description below. |
| Part B | Experimental | Drug: Intermittent dosing of AZD5363This part of the study will not be conducted following a review of data from Part A. See intervention description below. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intermittent dosing of AZD5363Intermittent 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. | Drug | Part A Group 1 Intermittent |
| Intermittent dosing of AZD5363Intermittent 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. | Drug | Part A Group 2 Intermittent |
| Intermittent dosing of AZD5363Intermittent 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. | Drug | Part B |
Primary outcome
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
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
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
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.
5 secondary outcomes
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.
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
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
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.
Parts A and B: Quality of life (QoL)
Time frame: QOL will be documented from date of randomization and for 12 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2014.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Stockman, MBCHB, PHD study director
AstraZeneca
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intermittent dosing of AZD5363 in people with Metastatic Castrate-Resistant Prostate Cancer (mCRPC), and Efficacy,, run by AstraZeneca at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2014.