An Open-label, Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With and Without SRC or MEK Inhibition on the Development of EMT in Prostate Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- N-cadherin and vimentin expression
Study Overview
Brief Summary
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in men. The purpose of this research study is to compare prostate cancers treated with hormone therapy versus prostate cancers treated with hormone therapy plus drugs that directly target cancer cells.
Detailed Description
Most prostate cancers respond to hormone therapy, also known as chemical castration. Unfortunately, castration resistance may occur in certain prostate cancers. Castration resistance or hormone refractory prostate cancer means that the cancer continues to progress as seen by progressively rising PSA and/or or an increase in tumor mass on bone scan, X-ray, CT scan or MRI despite previous hormonal therapy. The researchers are interested in understanding mechanisms of castration resistance in prostate cancer by analyzing prostate tissue before radical prostatectomy (from prostate biopsy tissue) and after radical prostatectomy (whole prostate specimen). They will look at the "molecular signature" of prostate cancer cells after hormone therapy to identify the key steps that the cancer cells undergo to become resistant to hormone therapy. In addition, the researchers will use other medications in addition to hormone therapy in order to block some of the key biochemical steps that are thought to mediate treatment resistance. This research will provide crucial information for the development of therapies that can improve the clinical outcome of patients with advanced prostate cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
AR inhibition only
AR inhibition only Group 1: degarelix + enzalutamide
Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.
Intervention: degarelix (Drug)
AR inhibition only
AR inhibition only Group 1: degarelix + enzalutamide
Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.
Intervention: enzalutamide (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
Intervention: degarelix (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
Intervention: enzalutamide (Drug)
AR inhibition plus MEK inhibition
AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide
In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.
Intervention: trametinib (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
Intervention: degarelix (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
Intervention: enzalutamide (Drug)
AR inhibition plus SRC inhibition
AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide
In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.
Intervention: dasatinib (Drug)
Outcomes
Primary Outcomes
N-cadherin and vimentin expression
Time Frame: Prostatectomy will occur during the 2 week "window" between 6 and 8 weeks after enrollment
The primary outcome of N-cadherin and vimentin expression will be measured in post-treatment RP specimens. Comparisons amongst the various treatment groups (post-treatment inter-group) will be performed after all data have been collected.
Secondary Outcomes
No secondary outcomes reported