Hormonal Therapy and Chemotherapy Followed by Prostatectomy in Patients With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Degarelix; Doxorubicin; Ketoconazole; Docetaxel; Estramustine
Intervention description: Subcutaneous injection, once/month for 4 months; 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5; 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5; 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6; 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Intervention MeSH terms: Ketoconazole; Docetaxel; Doxorubicin; Estramustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Prostate Cancer; Neoadjuvant; Hormone therapy; ADT; Androgen Deprivation Therapy; Chemotherapy; Radical Prostatectomy

Summary:

      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
      prostate removal.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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
             abdomen.

          -  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.

        Exclusion Criteria:

          -  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
             disorder.

          -  Severe gastrointestinal bleeding within 12 weeks of treatment with ADT and
             chemotherapy

          -  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