Study of Olaparib (± Degarelix) Given to Men With Intermediate/High Risk Prostate Cancer Before Prostatectomy

Sponsor
Cambridge University Hospitals NHS Foundation Trust
Study ID
NCT02324998
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
MALE
Age
18 Years - 73 Years
Healthy Volunteers
Not accepted

Interventions

  • Olaparib — DRUG
    PARP Inhibitor
  • Degarelix — DRUG
    Gonadotrophin releasing hormone blocker

Study Details

Despite recent advances in the treatment of Castrate-Resistant Prostate Cancer (CRPC), there remains an unmet medical need to identify and optimise additional treatment for those patients with early prostate cancer who are at greatest risk of relapse following first-line treatment with curative intent. This is a phase I study investigating the feasibility and tolerability of a short course of neoadjuvant treatment with olaparib, either as a monotherapy or in combination with degarelix) given in the window-of-opportunity prior to radical prostatectomy in men with early, localised intermediate-/high- risk prostate cancer. Our primary objective is to determine the pharmacodynamic biomarker effects of olaparib (a PARP inhibitor) in this patient population. Participants will receive either single agent olaparib or olaparib in combination with degarelix (androgen deprivation) for two weeks prior to routine radical prostatectomy. We will use immunohistochemistry to quantify changes in the levels of biomarkers of PARP inhibition, e.g. PAR, gamma H2AX, pH2A(s129) and Rad51 foci, using tumour samples taken at baseline and at the time of radical prostatectomy. An intra-operative prostate biopsy will permit us to examine biomarker variability between the samples. The incidence and severity of Adverse Events will be documented and we will assess the number of trial participants who undergo surgery on schedule. We will assess preliminary evidence of tumour response, e.g. pathological changes and Prostate Specific Antigen (PSA). We also intend to investigate changes to the ctDNA profile by comparing blood samples collected throughout the study.

Key Dates

Start date
Dec 31, 2016
Status verified
Aug 2019
Primary completion
May 31, 2019
Completion
May 31, 2019

Study Design

Enrollment
20 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER

Arms

  • Experimental: Group A
    Olaparib Monotherapy
  • Experimental: Group B
    Olaparib in combination with degarelix

Primary Outcome Measure

Determination of PARP Inhibition [ Time Frame: Two week olaparib therapy (alone or in combination with degarelix) ]

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