This is a study for men who have locally-advanced prostate cancer and are eligible to undergo
prostatectomy. Standard treatment is prostatectomy alone, but there is a chance that cancer
may spread to other organs in the future, even after the prostate is removed. If this were to
occur, standard treatment would be androgen deprivation therapy (ADT; hormone therapy that
blocks testosterone) plus chemotherapy. Clinical trials suggest that neoadjuvant treatment
(treatment given before primary therapy) may prevent a recurrence. The purpose of this
research study is to assess the safety and benefit of ADT plus chemotherapy given before
This is an open-label, single-arm study of neoadjuvant ADT and chemotherapy in subjects with
non-metastatic, locally-advanced prostate cancer who are eligible for radical prostatectomy.
Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles
of chemotherapy. Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2
weeks of rest. In the absence of toxicity or disease progression, patients will receive 2
cycles of treatment prior to radical prostatectomy.
The primary endpoint will be complete or near-complete pathologic response.
Safety will be assessed on any patient receiving at least one dose of study drug by the
reporting of adverse events, vital signs and by the assessment of findings on physical exam
and routine safety laboratory determinations. The severity of adverse events and certain
abnormal laboratory findings will be assessed according to the NCI CTCAE V4.03.
Laboratory-based studies will evaluate the following:
- Complete metabolic profile
o BUN, creatinine, alkaline phosphatase, ALT/AST, total bilirubin, LDH, calcium,
albumin, glucose, magnesium, uric acid, phosphorous
o Sodium, potassium, chloride, CO2 content
- CBC with differential, platelet count
- PT, INR, PTT
- Pathologic proof of prostatic adenocarcinoma without evidence of regional and/or
distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason 8-10)
on initial biopsy, clinical stage T2b-T2c with Gleason grade 7 (4+3), or clinical
stage T3. No neuroendocrine differentiation or small cell features.
- Recent (<6 weeks prior to study entry) negative bone scan and CT of the chest and
- Appropriate surgical candidate for radical prostatectomy and a performance status of
<2 (ECOG scale).
- Adequate bone marrow function as defined as an absolute peripheral granulocyte count
>1500 and platelet count >100,000.
- Adequate hepatic function per the following criteria:
- Albumin ≥2.8 g/dL
- AST and ALT ≤5 x ULN
- Total bilirubin <2 mg/dL
- Adequate renal function per the following criteria:
o Serum creatinine ≤1.5 x ULN
- Normal coagulation profile (INR ≤ 1.5, aPTT ≤ 1.5 x ULN for the lab) and no history of
substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to
local use only (for control of central line patency).
- Age ≥ 18 years
- Written informed consent to participate in this study.
- Prostatic adenocarcinoma with neuroendocrine differentiation or small cell features
- Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1
week of first ADT and chemotherapy treatment
- Previous or current hormonal treatment, chemotherapy, radiation therapy,
immunotherapy, or investigational study drug.
- Unable to tolerate multiparametric MRI or is contraindicated.
- Patients not appropriate surgical candidates for radical prostatectomy based on the
evaluation of coexistent medical diseases and competing causes of death.
- Patients with uncontrolled cardiac, hepatic, renal, or neurologic/psychiatric
- Severe gastrointestinal bleeding within 12 weeks of treatment with ADT and
- Patients who are HIV positive or have chronic hepatitis B or C infections.
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of
congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a 2D
echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months of
enrollment demonstrates a left ventricular ejection fraction >45%.
- Sensory neuropathy grade >1.
- History of another malignancy within the previous 5 years other than curatively
treated non-melanoma skin cancer.
- Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic
corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4
weeks of enrollment.
- Any other condition, including concurrent medical condition, social circumstance or
drug dependency, which in the opinion of the investigator could compromise patient
safety and/or compliance with study requirements