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, Richards, Renee S., Kienzle, Nicholas, Lu, Macy, Brereton, Ian, Samaratunga, Hema, Perry-Keene, Joanna, Payton, Diane, Oyama, Chikara, Doi, Suhail A., Lavin, Martin F. and Gardiner, Robert A. (2016) 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. Contemporary Clinical Trials, 50 16-20. doi:10.1016/j.cct.2016.06.014

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ408799_OA.pdf Full text (open access) application/pdf 398.17KB 0

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.
Title 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
Journal name Contemporary Clinical Trials   Check publisher's open access policy
ISSN 1559-2030
1551-7144
Publication date 2016-09-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.cct.2016.06.014
Open Access Status File (Author Post-print)
Volume 50
Start page 16
End page 20
Total pages 5
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Subject 2700 Medicine
2736 Pharmacology (medical)
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.
Formatted 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.
Keyword Atorvastatin
Biomarkers
Clinical trial
Metabolomics
Metformin
Prostate cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 11 Oct 2016, 11:30:56 EST by System User on behalf of Learning and Research Services (UQ Library)