Hydroxychloroquine to Increase Tumor Suppressor PAR-4 Levels in Oligometastatic Prostate Cancer

Summary

Treatment of recurrent oligometastatic prostate cancer may be enhanced by the addition of Hydroxychloroquine to the current treatment regimens. Potential benefits of Hydroxychloroquine include delayed disease progression and delayed initiation of androgen deprivation therapy (ADT), thus lessening morbidity, distressing side effects, and improving functioning and quality of life in men with recurrent prostate cancer. Building on prior research at Markey, patients recently diagnosed with recurrent oligometastatic prostate cancer will be approached about participating in this study. Per standard of care, these patients undergo either surgery or radiation, in addition participants of this clinical trial will also receive Hydroxychloroquine (400 mg per day, oral medication) for 3 months. It is expected that a participant will exhibit a 50% increase of tumor suppressor PAR-4, as well as few, if any, negative side effects from Hydroxychloroquine.

Timeline

Start

2019-12-03

Primary completion

2024-03-08

Completion

2024-03-08

Publications

• Background Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017 Jan;14(1):15-25. doi: 10.1038/nrurol.2016.175. Epub 2016 Oct 11.
• Background Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009 Jun 1;115(11):2388-99. doi: 10.1002/cncr.24283.
• Background Burikhanov R, Shrestha-Bhattarai T, Hebbar N, Qiu S, Zhao Y, Zambetti GP, Rangnekar VM. Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4. Cell Rep. 2014 Jan 30;6(2):271-7. doi: 10.1016/j.celrep.2013.12.020. Epub 2014 Jan 9.
• Background Hebbar N, Wang C, Rangnekar VM. Mechanisms of apoptosis by the tumor suppressor Par-4. J Cell Physiol. 2012 Dec;227(12):3715-21. doi: 10.1002/jcp.24098.
• Background Kimura T, Takabatake Y, Takahashi A, Isaka Y. Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer Res. 2013 Jan 1;73(1):3-7. doi: 10.1158/0008-5472.CAN-12-2464.
• Background Ratikan JA, Sayre JW, Schaue D. Chloroquine engages the immune system to eradicate irradiated breast tumors in mice. Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):761-8. doi: 10.1016/j.ijrobp.2013.07.024.
• Background Burikhanov R, Hebbar N, Noothi SK, Shukla N, Sledziona J, Araujo N, Kudrimoti M, Wang QJ, Watt DS, Welch DR, Maranchie J, Harada A, Rangnekar VM. Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis. Cell Rep. 2017 Jan 10;18(2):508-519. doi: 10.1016/j.celrep.2016.12.051.
• Background Wang P, Burikhanov R, Jayswal R, Weiss HL, Arnold SM, Villano JL, Rangnekar VM. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018 May;9(5-6):190-197. doi: 10.18632/genesandcancer.181.

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