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.

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.

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 8weeks, 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 progression, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken alongside quality of life and psychosocial outcome assessments.

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.

Contemporary clinical trials. 2016 Jun 28 [Epub ahead of print]

Matthew J Roberts, John W Yaxley, Geoffrey D Coughlin, Troy R J Gianduzzo, Rachel C Esler, Nigel T Dunglison, Suzanne K Chambers, Robyn J Medcraft, Clement W K Chow, Horst Joachim Schirra, Renee S Richards, Nicholas Kienzle, Macy Lu, Ian Brereton, Hema Samaratunga, Joanna Perry-Keene, Diane Payton, Chikara Oyama, Suhail A Doi, Martin F Lavin, Robert A Gardiner

The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia; School of Medicine, The University of Queensland, Herston, Qld, 4006, Australia; The Centre for Advanced Imaging, The University of Queensland, St. Lucia, Brisbane, Qld 4072, Australia. Electronic address: ., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia; School of Medicine, The University of Queensland, Herston, Qld, 4006, Australia. Electronic address: ., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia; Griffith Health Institute, Griffith University, Gold Coast, Qld 4222, Australia. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia. Electronic address: ., The Centre for Advanced Imaging, The University of Queensland, St. Lucia, Brisbane, Qld 4072, Australia. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Medical Imaging, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Medical Imaging, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia. Electronic address: ., The Centre for Advanced Imaging, The University of Queensland, St. Lucia, Brisbane, Qld 4072, Australia. Electronic address: ., School of Medicine, The University of Queensland, Herston, Qld, 4006, Australia; Aquesta Pathology, PO, Box 1878, Toowong DC, Brisbane, Qld, 4066, Australia. Electronic address: ., Anatomical Pathology, Pathology Queensland, Herston, Brisbane, Qld, 4029, Australia. Electronic address: ., Anatomical Pathology, Pathology Queensland, Herston, Brisbane, Qld, 4029, Australia. Electronic address: ., Department of Urology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: ., Research School of Population Health, The Australian National University, Canberra, ACT, Australia; School of Agricultural, Computational and Environmental Sciences, University of Southern Queensland, Toowoomba, Australia; College of Medicine, Qatar University, Doha, Qatar. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia. Electronic address: ., The University of Queensland, Centre for Clinical Research, Building 71/918, RBWH, Herston, Brisbane, Qld, 4029, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, 4029, Australia; School of Medicine, The University of Queensland, Herston, Qld, 4006, Australia; Edith Cowan University, Joondalup, WA, 6027, Australia. Electronic address: .