Clinical trial NCT00024167
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate stage IV prostate cancer recurrent prostate cancer Strontium-89 Induction Chemotherapy Androgen-Independent Prostate Cancer
Sponsor: M.D. Anderson Cancer Center
Start date: 2002-04-01; Completion date: 2014-09-01
Enrollment: 265 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether chemotherapy is more effective with or without strontium-89 in treating bone metastases.

PURPOSE: This randomized phase III trial is studying giving chemotherapy together with strontium-89 to see how well it works compared to chemotherapy alone in treating patients with prostate cancer that has spread to the bone.

Detailed description:
OBJECTIVES:

* Compare the effectiveness, in terms of overall survival, of consolidation therapy with or without strontium chloride Sr 89 after induction chemotherapy in patients with androgen-independent prostate cancer.

OUTLINE: This is a randomized study. Patients are stratified according to type of induction chemotherapy (KAVE vs prednisone and docetaxel), number of bony metastases (no more than 20 vs more than 20), Eastern Cooperative Oncology (ECOG) performance status (0-1 vs 2-3), and use of zoledronate (yes vs no).

* Induction therapy: Patients receive 1 of 2 induction therapy regimens.

  * Regimen A (KAVE): Patients receive doxorubicin IV over 24 hours on day 1 and oral ketoconazole three times daily on days 1-7 of weeks 1, 3, and 5. Patients receive vinblastine IV over 30 minutes on day 1 and oral estramustine three times daily on days 1-7 of weeks 2, 4, and 6. Patients receive no treatment on weeks 7 and 8. Treatment repeats every 8 weeks for at least 2 courses\* in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients continue to receive oral ketoconazole three times daily until disease progression.

* Regimen B (prednisone and docetaxel): Patients receive oral prednisone twice daily on days 1-21 (days 1-14 of course 5 only) and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity.

  * Consolidation therapy: Patients with a prostate-specific antigen (PSA) response (at least 50% decline in PSA level from baseline at week 16 OR at least 2 PSA levels decreased at least 50% from baseline) are randomized to 1 of 2 consolidation treatment arms.
* Arm I: Patients receive doxorubicin IV over 24 hours once weekly for 6 weeks plus strontium chloride Sr 89 IV once at the beginning of chemotherapy.
* Arm II: Patients receive doxorubicin as in arm I. Patients are followed every 4 weeks until PSA progression and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 480 patients (240 randomized) will be accrued for this study within 48 months.

Arms: arm 1: Doxorubicin IV over 24 hours day 1; Oral ketoconazole 3 x daily on days 1-7 of weeks 1, 3, and 5; Vinblastine IV over 30 minutes Day 1, oral Estramustine 3 x daily on Days 1-7 of weeks 2, 4, and 6. arm 2: Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1. arm 3: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy. arm 4: Doxorubicin as in Consolidation arm I.
Interventions: intervention 1: Docetaxel intervention 2: Doxorubicin hydrochloride intervention 3: Estramustine phosphate sodium intervention 4: Ketoconazole intervention 5: Prednisone intervention 6: Vinblastine intervention 7: Strontium chloride Sr 89 intervention 8: Dexamethasone
Intervention descriptions: intervention 1: 75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks. intervention 2: 20 mg/m2 IV, day 1 on Weeks 1, 3, 5 intervention 3: 140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6 intervention 4: 400 mg orally (po) 3 x day, Days 1 through 7 intervention 5: 5 mg orally 2 x daily, weeks 1-14 intervention 6: 4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6 intervention 7: One dose (4 mCi total dose) IV intervention 8: 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.

Protocol documents: