Randomized trial assessing induction of double strand breaks with androgen receptor partial agonist in patients on androgen suppression
Johns Hopkins Kimmel Cancer Center in Baltimore
Primary objective:To confirm DNA double strand breaks occur in prostate cancer tissue following pulse-dose flutamide administration in patients who are androgen suppressed, as compared to control patients receiving placebo.Exploratory objective:To explore the feasibility of detecting cancer-specific alterations in DNA methylation and structure within urine and plasma, and the kinetics for these measures when compared with PSA values and clinical response. We will examine whether prostate cancer specific DNA methylation alterations at a panel of frequently hypermethylated loci (e.g. GSTP1, PTGS2, MDR1, APC, RARbeta, gene promoters) can be used as a DNA based biomarker for tracking therapeutic response.
Inclusion criteria - Histologically confirmed, localized (M0) adenocarcinoma of the prostate- Clinical stages T1c – T3b, Mx or M0 - At least one biopsy core with Gleason 7 or higher disease- The patient has decided to undergo brachytherapy plus androgen suppression as treatment modality for his prostate cancer (with or without supplemental external beam radiation)- Suitable volume of disease for biopsy, defined as one or more of the following:- mpMRI scan of the pelvis with equal to 1 identifiable lesion as being PI-RADS 4 or 5, plus minimum of at least 0.5cm in any dimensionOR- Clinically palpable disease corresponding to (ipsilateral to) any involved core on biopsy- Signed study-specific consent form prior to registrationExclusion criteria -Known hypersensitivity or allergic response to flutamide- Severe hepatic impairment (serum ALT level greater than 2x normal or serum AST level greater than 2x normal) - Known hypogonadism (serum total testosterone less than 150 ng/dL), or treatment with testosterone supplementation therapy within 12 months prior to enrollment
This is a prospective single center two phase study to assess the efficacy of single dose flutamide in creating double strand breaks in prostate cancer with patients receiving central androgen suppression and brachytherapy. Subjects are randomized to 2:1 ratio for total of 18 patients randomized receiving flutamide and 6 patients receiving placebo. Thus total patients including both phases will be 24 patients .
03/05/2019 05:03 AM