Last updated on August 2018

Bipolar Androgen Therapy in Metastatic Castrate Resistant Prostate Cancer With Homologous Recombination Deficiency

Brief description of study

The purpose of this study is to determine the efficacy of BAT in men with metastatic castrate-resistant prostate cancer (mCRPC) and homologous recombination deficiency (HRD). Bipolar androgen therapy will be administered to men confirmed to have HRD on tumour tissue and/or circulating tumour DNA analysis on pre-screening.

Detailed Study Description

Androgen deprivation therapy (ADT) remains the mainstay of prostate cancer treatment. Though an effective therapy initially, the side effects of ADT are numerous and treatment resistance is inevitable. Castrate-refractory prostate cancer (CRPC) progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signalling despite castrate levels of androgens.

The concept of cycling between supra- and sub physiological levels of testosterone has been tested recently in studies of "bipolar androgen therapy" (BAT) in which patients are given high dose testosterone in combination with androgen deprivation therapy (ADT) via an LHRH agonist/antagonist. Studies of BAT using IM testosterone have been promising both in terms of PSA responses and quality of life improvements. Additionally, these early phase studies suggest the potential for re-sensitisation to novel anti-androgen therapies.

Though responses have been positive in these early studies a proportion of men fail to respond and data to guide patient selection is lacking. There are data to suggest that patients with DNA repair deficits may be particularly responsive to BAT. Whether these changes serve as predictors of response is unknown as the effect of BAT on the tumour, its microenvironment and peripheral circulating tumour DNA has not been studied in detail. Information on treatment effects may be key to appropriate patient selection for this treatment.

The aim of this study is to assess homologous repair deficiency as a predictive biomarker of response to bipolar androgen therapy in men with metastatic castrate-refractory prostate cancer and to study the effects of this treatment on ctDNA and intra-tumoural gene expression.

Clinical Study Identifier: NCT03522064

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Recruitment Status: Open

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