Trial Information

A Phase III Randomized Study of Patients With High Risk, Hormone-Naive Prostate Cancer: Androgen Blockade With 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade With Delayed Chemotherapy

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 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.