Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as
      luteinizing hormone-releasing hormone agonist, flutamide, and bicalutamide may stop the
      adrenal glands from producing androgens. Drugs used in chemotherapy work in different ways to
      stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with
      chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy given at the
      same time as hormone therapy is more effective than chemotherapy given after hormone therapy
      in treating prostate cancer.

      PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given at the
      same time as hormone therapy with that of chemotherapy given after hormone therapy in
      treating patients who have prostate cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the survival of patients with high-risk hormone-naive prostate cancer treated
           with androgen blockade with concurrent chemotherapy vs delayed chemotherapy.

      Secondary

        -  Compare biochemical control in patients treated with these regimens.

        -  Determine the toxicity of these regimens in these patients.

        -  Compare the time to clinical failure, as measured by progression on bone scan or CT scan
           or a prostate-specific antigen (PSA) doubling time of ≤ 32 weeks, in patients treated
           with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior
      therapy (surgery vs radiotherapy and/or brachytherapy vs both), original combined Gleason
      score (6 vs 7 vs 8-10), and prior vaccine therapy (yes vs no). Patients are randomized to 1
      of 2 treatment arms.

        -  Arm I: Patients receive androgen blockade (AB) comprising a luteinizing-hormone
           releasing-hormone agonist continuously and oral flutamide or oral bicalutamide once
           daily for at least 1 month. Within 4 weeks of initiation of AB, patients begin
           chemotherapy. Patients receive 1, and only 1, of the following chemotherapy regimens:

             -  Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and
                docetaxel IV on day 3. Treatment repeats every 21 days for 4 courses in the absence
                of disease progression or unacceptable toxicity.

             -  Regimen B: Patients receive oral estramustine 3 times daily on days 1-5 and
                paclitaxel IV on days 3, 10, 17, 24, 31, and 38. Treatment repeats every 56 days
                for 4 courses in the absence of disease progression or unacceptable toxicity.

             -  Regimen C: Patients receive oral ketoconazole 3 times daily on days 1-7, 15-21, and
                29-35; doxorubicin IV on days 1, 15, and 29; vinblastine IV on days 8, 22, and 36;
                and oral estramustine 3 times daily on days 8-14, 22-28, and 36-42. Treatment
                repeats every 56 days for 4 courses in the absence of disease progression or
                unacceptable toxicity.

             -  Regimen D: Patients receive oral estramustine 3 times daily on days 1-4 and
                docetaxel IV over 1 hour on days 3, 10, and 17. Treatment repeats every 28 days for
                4 courses in the absence of disease progression or unacceptable toxicity.

             -  Regimen E: Patients receive docetaxel IV on day 1. Treatment repeats every 21 days
                for 4 courses in the absence of disease progression or unacceptable toxicity.

             -  Regimen F: Patients receive docetaxel IV on days 1, 8, and 15. Treatment repeats
                every 28 days for 4 courses in the absence of disease progression or unacceptable
                toxicity.

             -  Regimen G: With approval from the protocol chair, patients may receive a regimen
                that has been demonstrated in a published phase II study to have at least a 50%
                response rate as measured by PSA decrease from baseline over 2 measurements 28 days
                apart or a decrease in measurable soft tissue disease by 50% in 2 dimensions.

        -  Arm II: Patients receive AB as in arm I. Patients continue with AB until clinical
           failure, at which time patients receive chemotherapy as in arm I. Patients who have a
           response may continue to receive chemotherapy beyond 4 courses.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 1,050 patients will be accrued for this study within 4-6 years.
    

Intervention name(s): bicalutamide; docetaxel; doxorubicin hydrochloride; estramustine phosphate sodium; flutamide; ketoconazole; paclitaxel; releasing hormone agonist therapy; vinblastine sulfate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ketoconazole; Vinblastine; Docetaxel; Doxorubicin; Liposomal doxorubicin; Bicalutamide; Flutamide; Estramustine; Hormones
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer