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Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol
Roberts, Matthew J. Yaxley, John W. Coughlin, Geoffrey D. Gianduzzo, Troy R. J. Esler, Rachel C. Dunglison, Nigel T. Chambers, Suzanne K. Medcraft, Robyn J. Chow, Clement W. K. Schirra, Horst Joachim
Roberts, Matthew J.
Yaxley, John W.
Coughlin, Geoffrey D.
Gianduzzo, Troy R. J.
Esler, Rachel C.
Dunglison, Nigel T.
Chambers, Suzanne K.
Medcraft, Robyn J.
Chow, Clement W. K.
Schirra, Horst Joachim
Author
Roberts, Matthew J.
Yaxley, John W.
Coughlin, Geoffrey D.
Gianduzzo, Troy R. J.
Esler, Rachel C.
Dunglison, Nigel T.
Chambers, Suzanne K.
Medcraft, Robyn J.
Chow, Clement W. K.
Schirra, Horst Joachim
Richards, Renee S.
Kienzle, Nicholas
Lu, Macy
Brereton, Ian
Samaratunga, Hema
Perry-Keene, Joanna
Payton, Diane
Oyama, Chikara
Doi, Suhail A.
Lavin, Martin F.
Gardiner, Robert A.
Yaxley, John W.
Coughlin, Geoffrey D.
Gianduzzo, Troy R. J.
Esler, Rachel C.
Dunglison, Nigel T.
Chambers, Suzanne K.
Medcraft, Robyn J.
Chow, Clement W. K.
Schirra, Horst Joachim
Richards, Renee S.
Kienzle, Nicholas
Lu, Macy
Brereton, Ian
Samaratunga, Hema
Perry-Keene, Joanna
Payton, Diane
Oyama, Chikara
Doi, Suhail A.
Lavin, Martin F.
Gardiner, Robert A.
Abstract
Background
Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa.
Methods/design
This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees.
Participants are being randomized into four groups: metformin with placebo; atorvastatin with placebo; metformin with atorvastatin; or placebo alone. Capsules are consumed for 8 weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in-vivo with those in seminal fluid and biopsied tissue.
The primary end point is biochemical evolution, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken.
Discussion
This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression.
Keywords
prostate cancer, atorvastatin, metformin, clinical trial, biomarkers, metabolomics
Date
2016
Type
Journal article
Journal
Contemporary Clinical Trials
Book
Volume
50
Issue
Page Range
16-20
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled