Prostate Cancer
Conditions
Keywords
prostate cancer, hormone therapy, radical prostatectomy
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.
Interventions
DRUGdegarelix
Every 4-week Treatment: A starting dose of 240 mg of Degarelix is taken subcutaneously (SQ) -placed under the skin by injection- the first month. Doses continue every 4 weeks at 80 mg SQ. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician.
DRUGenzalutamide
Once Daily Treatment: A starting dose of 160 mg of Enzalutamide is taken by mouth once daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician.
DRUGtrametinib
Once Daily Treatment: If randomized into Group 2, then 2mg of Trametinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician
DRUGdasatinib
Once Daily Treatment: If randomized into Group 3, then 100mg of Dasatinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician
Sponsors
Medivation, Inc.
GlaxoSmithKline
Prostate Cancer Foundation
Astellas Pharma Inc
Novartis
Jonsson Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(patients must meet all of the following inclusion criteria to participate in this study) 1. Willing and able to give informed consent. 2. Adenocarcinoma of the prostate with planned RP with curative intent as part of standard of care management plan. 3. Patient is a candidate for radical prostatectomy. 4. Tumor accessible to biopsy. 5. Age ≥ 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Estimated life expectancy of ≥ 6 months, 8. Adequate organ function: normal renal, liver, hematologic, coagulation and cardiac function: 1. Absolute neutrophil count \> 1,500/µL, or platelet count \> 100,000/µL, or hemoglobin \> 5.6 mmol/L (9 g/dL) at the Screening visit, 2. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) within the normal range at the Screening visit, 3. Creatinine \< 1.5 mg/dL at the Screening visit, 4. INR \< 1.3 (or \< 3 if on warfarin or other anticoagulants) at the Screening visit, 5. Albumin \> 30 g/L (3.0 g/dL) at the Screening visit, 6. Left ventricular ejection fraction (LVEF) ≥ LLN by ECHO or MUGA, 9. Patients with clinically localized adenocarcinoma of the prostate who are scheduled to undergo radical prostatectomy (RP) with curative intent and have the following clinico-pathologic features: (1) Gleason score sum ≥ 4+3 or any Gleason 5, (2) PSA \> 20, (3) clinical stage ≥ T3a (staging by MRI is allowed). 10. Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels, 11. Willing to abstain from procreative sex or partake in appropriate form of contraception. For the purpose of this study, condom use or abstinence will be required.
Exclusion criteria
(all candidates meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| N-cadherin and vimentin expression | 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. |
Countries
United States
Outcome results
None listed