Investigating the Effects of AZD2014 Therapy Given Prior to Radical Prostatectomy in Men With High Risk Prostate Cancer (CaNCaP02)
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|ClinicalTrials.gov Identifier: NCT02064608|
Recruitment Status : Completed
First Posted : February 17, 2014
Last Update Posted : July 17, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: AZD2014||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||June 2018|
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.
Other Name: AZ12729279
- 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.
- 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 ]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.
- To determine the severity of adverse events due to AZD2014 prior to radical prostatectomy [ Time Frame: 8 weeks unless further observation is clinically indicated ]The severity of all adverse events will graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
- To determine blood plasma concentration and pharmacokinetics of AZD2014. [ Time Frame: Following 15 days AZD2014 treatment ]On the day of radical prostatectomy surgery, participants will have up to four blood samples taken before and after their AZD2014 dose for pharmacokinetic analysis. These samples will be used to construct a concentration-time curve for AZD2014 in the blood.
- To measure the biological effects of AZD2014 treatment [ Time Frame: Following 15 days AZD2014 treatment ]Participants will be treated with AZD2014 for 15 days prior to radical prostatectomy surgery. The biological effects of AZD2014 treatment will be determined by analysis of prostate tumour biopsies and blood samples taken at baseline and following AZD2014 treatment.
- Exploratory endpoints [ Time Frame: Following 15 days AZD2014 treatment ]
The biological effects of AZD2014 on blood and prostate tumour samples will be investigated:
Histological markers of tumour cell proliferation, apoptosis and androgen receptor control of tumour metabolism will be measured.
Blood samples will be used to identify genetic changes in DNA, RNA and circulating tumor DNA caused by AZD2014 treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02064608
|Cambridge University Hospitals NHS Foundation Trust|
|Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ|
|Principal Investigator:||Simon C Pacey, MRCP, PhD||Cambridge University Hospitals NHS Foundation Trust|