Phase II study of enzalutamide (MDV3100) and gonadotropin-releasing hormone (GnRH) agonist before, during and after radiation therapy in treatment of patients with high-risk localized prostate cancer
- UT Southwestern-Clinical Translational Research Center (CTRC)
This is a single institution phase ii trial studying the safety and efficacy of combined enzalutamide and GnRH agonist therapy administered with eBRT for high-risk and locally advanced prostate cancer.
- Histologically proven adenocarcinoma of the prostate obtained within 6 months of screening. Patients in whom a diagnosis of high-risk localized or locally-advanced prostatic adenocarcinoma is suspected based on a serum PSA > 20 ng/mL or clinical T3 disease by digital rectal examination, but who have not yet undergone diagnostic prostate biopsy, will be eligible for screening and initial MRI and targeted prostate cancer biopsies which will be obtained at the same time as diagnostic biopsies. Those patients in whom the diagnostic biopsies confirm prostatic adenocarcinoma will be permitted to continue with study treatment if they meet all additional eligibility criteria.
- Age >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Adequate organ and marrow function as defined below:
- leukocytes >= 3,000/mcL
- absolute neutrophil count >= 1,500/mcL
- platelets >= 100,000/mcl
- hemoglobin > 10 g/dL
- total bilirubin < 1.5 X institutional upper limit of normal (except for patients with documented Gilbert[Single Quote]s disease)
- AST(SGOT)/ALT(SPGT) <= 2.5 X institutional upper limit of normal
- creatinine < 1.5 X institutional upper limit of normal or estimated glomerular filtration rate < 45 mL/min/1.73m2, given the risk of nephrogenic systemic fibrosis when using gadolinium-based intravenous contrast agents in these subjects.
- serum testosterone > 100 ng/dL
- Men who are sexually active with female partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant following intercourse with a study participant during his participation in this study, she should inform her treating physician immediately, and the study principal investigator should be informed immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Patients must be candidates for long-term androgen deprivation in combination with EBRT for the treatment of high-risk or locally-advanced prostate cancer by the following criteria:
* High risk disease: T3a or Gleason 8-10 or serum PSA > 20 ng/mL
* Gleason 7 also allowed if > 50% of cores positive for cancer or PSA velocity > 2 ng/mL/year in preceding 12 months
* Locally advanced (very high risk) disease: T3b-T4
- > 3 core biopsies positive for prostate cancer, minimum 6 core biopsies obtained
- Patients may have radiographic evidence of metastasis in regional lymph nodes (N1 disease as defined by the National Comprehensive Cancer Network Prostate Cancer Guideline Verson 3.2012) at the discretion of the treating physicians, if regional lymph nodes can be included in the planned radiation field.
- Participants in the study must permit targeted prostate biopsy prior to initiation of study treatment and at the time of fiducial marker placement
- Able and willing to provide written authorization for use and release of health and research study information
- Ability to understand and the willingness to sign a written informed consent.