Prostate CancerPhase 1CaNCaP02NCT02064608
Investigating the Effects of AZD2014 Therapy Given Prior to Radical Prostatectomy in Men With High Risk Prostate Cancer
A Phase 1 study testing AZD2014 in people with Prostate Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Patients with localised prostate cancer can be treated by radical prostatectomy (prostate gland removal surgery) or radiotherapy. Around 15% of men with prostate cancer are diagnosed with high risk disease meaning they are more likely to suffer treatment failure, disease progression and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- AZD2014
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2014to Jun 2018
- 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
- Men aged 18 years old or older
- ECOG performance status of 0 or 1
- Clinical diagnosis of Intermediate (one or more of stage T2, or PSA >10ng/mL, or Gleason score of at least 7) or High Risk Prostate Cancer (one or more of stage T2c, or PSA >20ng/mL, or Gleason score of at least 8)
- Patient suitable for radical prostatectomy, following discussion at specialist MDT and subsequent review by surgical team
- Willing to use barrier contraceptive method, e.g. condom \& spermicide
- Adequate bone marrow reserve or organ function (as specified in the study protocol)
- Normal chest radiograph and oxygen saturations, OR normal CT thorax
Who cannot join
- Contraindication to AZD2014 (as specified in the study protocol)
- Patients who have experienced any of the following procedures in the past 12 months: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; congestive heart failure (New York Heart Association grade of 2 or above); ventricular arrhythmias requiring continuous therapy; supraventricular arrhythmias including atrial fibrillation, which are uncontrolled; haemorrhagic or thrombotic stroke including transient ischaemic attacks or any other CNS bleeding.
- Previous chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents and/or investigational agents within 28 days of starting study treatment.
- Major surgery within 4 weeks prior to study entry (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study
- Potent or moderate inhibitors and inducers of CYP2C8 if taken within the stated wash-out period: Gemfibrozil, trimethoprim, glitazones, montelukast, deferasirox and quercetin (1-week minimum wash out period)
- Any haematopoietic growth factors, e.g. G-CSF, GM-CSF, within 4 weeks prior to receiving study drug
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- As judged by the Investigator, any evidence of severe or uncontrolled systemic disease (as specified in the study protocol)
- Abnormal ECHO or MUGA at baseline
- Mean resting QTc of 470msec or above (as per local reading)
- Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation, or risk of arrythmic events (examples specified in study protocol). History of Torsades de Pointes.
- Patients with Diabetes Type I or uncontrolled Type II as judged by the investigator
- Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A Phase 1 Window of Opportunity Study Investigating the Pharmacodynamic Biomarker Effects of AZD2014 (an mTOR1/2 Inhibitor) Given Prior to Radical Prostatectomy
Patients with localised prostate cancer can be treated by radical prostatectomy (prostate gland removal surgery) or radiotherapy. Around 15% of men with prostate cancer are diagnosed with high risk disease meaning they are more likely to suffer treatment failure, disease progression and mortality. To date little progress has been made towards identifying effective treatment strategies that might delay or prevent disease recurrence in this patient population. Better identification of patients at high risk of relapse and improvements in therapy are therefore research priorities.
A protein named Mammalian Target of Rapamycin (mTOR) is known to play an important role in the development of prostate cancer. mTOR forms two protein complexes (mTORC1 and mTORC2) and sends signals helping cancer cells to grow while controlling their energy use. Blocking the function of mTOR, with an inhibitor such as AZD2014, might shut down the supply of energy supply to tumour cells leading to reduced cell growth and potentially slowing the progression of the disease.
The purpose of this study is to investigate the molecular pharmacology of AZD2014 treatment given to patients with prostate cancer prior to radical prostatectomy. The feasibility, safety and tolerability of a short course of AZD2014 will also be assessed.
Read the detailed description
Eligible patients will be required to take 50mg AZD2014 tablets twice daily for 15 days prior to radical prostatectomy.
Immunohistochemistry will be carried out on prostate tumour biopsies taken at baseline and at radical prostatectomy in order to detect phosphorylated biomarkers of mTOR signalling and determine the amount of mTORC1 and mTORC2 signalling inhibition caused by AZD2014 treatment.
On the day of radical prostatectomy, blood samples will be collected pre- and at specified times post- dose for pharmacokinetic analyses.
Additional blood samples will be collected to study any genetic changes to the DNA, RNA and circulating tumour DNA (ctDNA) which may have been caused by AZD2014 treatment.
Refer to the "outcome measures" section for further information.
- Conditions
- Prostate Cancer
- Being tested
- AZD2014
- Keywords
- Prostate, Cancer, Prostate Cancer, High Risk, Intermediate Risk, Early disease, Neoadjuvant treatment, Radical Prostatectomy
- Medical subject headings
- Prostatic Neoplasms, Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2014Drug
Also called AZ12729279
mTOR inhibitor
| Study group | Role | What they receive |
|---|---|---|
| AZD2014 | Experimental | This is a single arm study whereby a cohort of 20 patients with early high risk prostate cancer will be treated with a 15-day course of AZD2014 (mTOR inhibitor) treatment prior to radical prostatectomy. Receives: Drug: AZD2014 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure the amount of inhibition (percentage change from baseline) in mTORC1 and mTORC2 signalling in tumour samples from men with early, high-risk prostate cancer after AZD2014 treatment
Participants will be treated with AZD2014 for 15 days prior to radical prostatectomy surgery. To assess the amount of mTORC1 and mTORC2 inhibition caused by AZD2014 treatment, phosphorylated signalling biomarkers (namely p4EBP1, pS6 and pAKT) will be detected by immunohistochemistry and quantified. The amount of mTORC1 and mTORC2 signalling inhibition will be determined by comparison of prostate tumour biopsies taken at baseline (time of diagnosis) and following AZD2014 treatment. An intra-operative prostate biopsy will also be taken in order to evaluate variability between samples.
Measured: 2 weeks
Secondary outcomes (2)
To determine the incidence of adverse events due to AZD2014 given prior to radical prostatectomy
In order to assess the safety and feasibility of AZD2014 treatment prior to radical prostatectomy, a record will be kept of all adverse events experienced by the participants. Adverse events will be detailed by the study team when the participant attends inpatient/outpatient hospital visits and the participant will also be required to document their adverse events in a patient diary. Adverse events will be recorded for the duration of study treatment and for six weeks following treatment.
Measured: 8 weeks unless further observation is clinically indicated
To determine the severity of adverse events due to AZD2014 prior to radical prostatectomy
The severity of all adverse events will graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Measured: 8 weeks unless further observation is clinically indicated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2016
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Simon C Pacey, MRCP, PhD, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02064608
- Sponsor's protocol ID
- CANCAP02
- Other IDs
- 2014-000214-56, 2014
- Acronym
- CaNCaP02
- Status last verified
- Jul 2019
- First submitted
- 14 Feb 2014
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Window of Opportunity Study Investigating the Pharmacodynamic Biomarker Effects of AZD2014 (an mTOR1/2 Inhibitor) Given Prior to Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT02064608
- Acronym / sponsor ID
- CaNCaP02 / CANCAP02
- Conditions
- Prostate Cancer
- Keywords
- Prostate, Cancer, Prostate Cancer, High Risk, Intermediate Risk, Early disease, Neoadjuvant treatment, Radical Prostatectomy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Oct 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 17 Feb 2014 (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.
Patients with localised prostate cancer can be treated by radical prostatectomy (prostate gland removal surgery) or radiotherapy. Around 15% of men with prostate cancer are diagnosed with high risk disease meaning they are more likely to suffer treatment failure, disease progression and mortality. To date little progress has been made towards identifying effective treatment strategies that might delay or prevent disease recurrence in this patient population. Better identification of patients at high risk of relapse and improvements in therapy are therefore research priorities.
A protein named Mammalian Target of Rapamycin (mTOR) is known to play an important role in the development of prostate cancer. mTOR forms two protein complexes (mTORC1 and mTORC2) and sends signals helping cancer cells to grow while controlling their energy use. Blocking the function of mTOR, with an inhibitor such as AZD2014, might shut down the supply of energy supply to tumour cells leading to reduced cell growth and potentially slowing the progression of the disease.
The purpose of this study is to investigate the molecular pharmacology of AZD2014 treatment given to patients with prostate cancer prior to radical prostatectomy. The feasibility, safety and tolerability of a short course of AZD2014 will also be assessed.
Detailed description
Eligible patients will be required to take 50mg AZD2014 tablets twice daily for 15 days prior to radical prostatectomy.
Immunohistochemistry will be carried out on prostate tumour biopsies taken at baseline and at radical prostatectomy in order to detect phosphorylated biomarkers of mTOR signalling and determine the amount of mTORC1 and mTORC2 signalling inhibition caused by AZD2014 treatment.
On the day of radical prostatectomy, blood samples will be collected pre- and at specified times post- dose for pharmacokinetic analyses.
Additional blood samples will be collected to study any genetic changes to the DNA, RNA and circulating tumour DNA (ctDNA) which may have been caused by AZD2014 treatment.
Refer to the "outcome measures" section for further information.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD2014 | Experimental | Drug: AZD2014This is a single arm study whereby a cohort of 20 patients with early high risk prostate cancer will be treated with a 15-day course of AZD2014 (mTOR inhibitor) treatment prior to radical prostatectomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men aged 18 years old or older
- ECOG performance status of 0 or 1
- Clinical diagnosis of Intermediate (one or more of stage T2, or PSA >10ng/mL, or Gleason score of at least 7) or High Risk Prostate Cancer (one or more of stage T2c, or PSA >20ng/mL, or Gleason score of at least 8)
- Patient suitable for radical prostatectomy, following discussion at specialist MDT and subsequent review by surgical team
- Willing to use barrier contraceptive method, e.g. condom \& spermicide
Key exclusion criteria (13 listed)
- Contraindication to AZD2014 (as specified in the study protocol)
- Patients who have experienced any of the following procedures in the past 12 months: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; congestive heart failure (New York Heart Association grade of 2 or above); ventricular arrhythmias requiring continuous therapy; supraventricular arrhythmias including atrial fibrillation, which are uncontrolled; haemorrhagic or thrombotic stroke including transient ischaemic attacks or any other CNS bleeding.
- Previous chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents and/or investigational agents within 28 days of starting study treatment.
- Major surgery within 4 weeks prior to study entry (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study
- Potent or moderate inhibitors and inducers of CYP2C8 if taken within the stated wash-out period: Gemfibrozil, trimethoprim, glitazones, montelukast, deferasirox and quercetin (1-week minimum wash out period)
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 |
|---|---|---|
| AZD2014Also: AZ12729279mTOR inhibitor | Drug | AZD2014 |
Primary outcome
To measure the amount of inhibition (percentage change from baseline) in mTORC1 and mTORC2 signalling in tumour samples from men with early, high-risk prostate cancer after AZD2014 treatment
Time frame: 2 weeks
Participants will be treated with AZD2014 for 15 days prior to radical prostatectomy surgery. To assess the amount of mTORC1 and mTORC2 inhibition caused by AZD2014 treatment, phosphorylated signalling biomarkers (namely p4EBP1, pS6 and pAKT) will be detected by immunohistochemistry and quantified. The amount of mTORC1 and mTORC2 signalling inhibition will be determined by comparison of prostate tumour biopsies taken at baseline (time of diagnosis) and following AZD2014 treatment. An intra-operative prostate biopsy will also be taken in order to evaluate variability between samples.
2 secondary outcomes
To determine the incidence of adverse events due to AZD2014 given prior to radical prostatectomy
Time frame: 8 weeks unless further observation is clinically indicated
To determine the severity of adverse events due to AZD2014 prior to radical prostatectomy
Time frame: 8 weeks unless further observation is clinically indicated
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 17 Jul 2019.
- Individual participant dataSharing planned: No
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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.
Simon C Pacey, MRCP, PhD principal investigator
Cambridge University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD2014 in people with Prostate Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 7 inclusion and 13 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 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
To measure the amount of inhibition (percentage change from baseline) in mTORC1 and mTORC2 signalling in tumour samples from men with early, high-risk prostate cancer after AZD2014 treatment (time frame: 2 weeks). 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 17 Jul 2019.