Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Doxorubicin; Ketoconazole; Docetaxel; Estramustine; Degarelix
Intervention description: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week); In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days); In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week); In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days); The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Intervention MeSH terms: Ketoconazole; Docetaxel; Doxorubicin; Estramustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Advanced; Local Failures

Summary:

      This study is for men who have prostate cancer and have failed local therapy or are not a
      candidate for prostatectomy or radiation therapy. The purpose of this research study is to
      assess the safety and benefit of androgen deprivation therapy (ADT, blocks hormones) plus
      chemotherapy. Degarelix is the hormone blocking drug that will be used. Doxorubicin,
      Ketoconazole, Docetaxel and Estramustine are the chemotherapy drugs that will be used. The
      drugs used in this study are approved by the Food and Drug Administration (FDA).

      Participants will be treated with ADT plus chemotherapy for three, four, or five 8-week
      cycles (12, 18, or 24 months). The number of cycles of chemotherapy they receive and the
      number of months they receive ADT will be based on their disease. The current standard
      treatment is ADT and chemotherapy. What differs in this research study is the cycling and
      combination of chemotherapy drugs chosen. The drugs chosen for this study have fewer side
      effects and are believed to provide maximum benefit.
    

Eligibility criteria:

        Inclusion criteria:

          -  Pathologic proof of adenocarcinoma of the prostate.

          -  Patients must belong to one of the following subsets:

          -  Prior local therapy

          -  Patients with Prostate Specific Antigen (PSA) recurrence following prostatectomy or
             radiation therapy who have no radiographic involvement. PSA doubling time ≤6 months.

          -  Nodal involvement only.

          -  Low volume bone disease: ≤3 metastases.

          -  Nodal involvement with associated bone involvement.

          -  High volume bone-visceral disease: Patients with >3 metastatic bone sites or visceral
             metastases.

          -  No prior definitive local therapy

          -  Tumors felt to be unresectable, not candidates for radiation therapy, and PSA elevated
             with biopsy-proven disease.

          -  Metastatic disease at presentation.

          -  Patients may have started ADT within 3 months of study entry.

          -  No previous cytotoxic therapy is allowed, including systemic irradiation with
             strontium-89, samarium, or radium-223.

          -  Previous definitive radiotherapy to one metastatic site is acceptable, provided that
             unirradiated sites remain. At least 8 weeks must have elapsed since radiation therapy
             to the pelvis. Patients having limited irradiation of a metastatic site are eligible 4
             weeks following radiation.

          -  Patients may have had previous exposure to ADT if it was given for ≤6 months to
             "downstage" the primary and provided that such therapy was completed at least 12
             months prior to entry into this study with a return of serum testosterone to ≥200
             ng/dL.

          -  Patients must be free of serious comorbidity and have a life expectancy of ≥3 years.

          -  Patients must have adequate physiologic reserves as evidenced by:

          -  Eastern Cooperative Oncology Group (ECOG) status of ≤2.

          -  Patients must have adequate bone marrow function: Platelets ≥100,000 cells/mm3,
             Hemoglobin ≥9.0 g/dL, and Absolute Neutrophil Count (ANC) ≥1,500 cells/mm3.

          -  Patients must have adequate renal function: creatinine ≤2 × upper limit of normal
             (ULN).

          -  Patients must have adequate liver function: Aspartate aminotransferase (AST) / Alanine
             transaminase (ALT) ≤2.5 × ULN; alkaline phosphatase <2.5 × ULN, unless bone metastasis
             is present in the absence of liver metastasis; and bilirubin < ULN or 1.5 mg/dl.

          -  No evidence of active ischemia on electrocardiogram (ECG) and documentation of
             ejection fraction (EF) ≥50%.

        Exclusion criteria:

          -  Patients must not have a second malignancy unless there is confidence of previous
             curative therapy.

          -  Patients with a recent history of transient ischemic attack (TIA) (within 6 months),
             who are requiring regular antianginal therapy, or who are having claudication
             sufficient to limit activity are not eligible. Patients with a previous history of
             deep venous thrombosis or pulmonary embolism (within 12 months) are not eligible

          -  Patients must not have a serious intercurrent medical or psychiatric illness,
             including serious active infection.

          -  Patients must not have sensory neuropathy > grade 1.