Trial Information

A Collaborative Randomized Phase III Trial: The Timing of Intervention With Androgen Deprivation in Prostate Cancer Patients With Rising PSA

OBJECTIVES:

Primary

- Compare overall survival (with acceptable morbidity) of patients with prostate cancer
treated with delayed vs immediate androgen deprivation therapy (ADT).

Secondary

- Compare cancer-specific survival of patients treated with these regimens.

- Compare clinical progression in patients treated with these regimens.

- Compare time to first androgen independence in patients treated with these regimens.

- Compare complication rate incidence and timing (e.g., cord compression or pathological
failure) in patients treated with these regimens.

- Compare treatment-related morbidity (including cognitive morbidity or osteoporosis) in
patients treated with these regimens.

- Compare quality of life of patients treated with these regimens.

- Determine prognostic factors for progression in patients treated with delayed ADT.

OUTLINE: This is a multicenter, randomized, controlled study. Patients in group 1 are
stratified according to prior therapy (prostatectomy vs radiotherapy vs prostatectomy and
radiotherapy), relapse-free interval (< 2 years vs ≥ 2 years), type of planned androgen
deprivation therapy (ADT) (continuous vs intermittent), and participating center. Patients
in group 2 are stratified according to type of planned ADT (continuous vs intermittent),
disease type (localized vs metastatic), and participating center. Patients in both groups
are randomized to 1 of 2 treatment arms.

- Arm I (delayed ADT): Beginning at least 2 years after study entry or after exhibiting
evidence of significant disease progression*, patients receive either continuous ADT OR
intermittent ADT comprising either bilateral orchiectomy OR luteinizing
hormone-releasing hormone agonist with or without oral antiandrogen therapy.

- Arm II (immediate ADT): Beginning immediately after randomization, patients receive
either continuous ADT OR intermittent ADT as in arm I.

NOTE: *Patients in group 1 begin delayed ADT at least 2 years after study entry unless 1 of
the following clinical criteria is present: prostate-specific antigen (PSA) doubling time of
< 12 months with PSA ≥ 10 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive
measurements obtained ≥ 2 months apart OR development of metastases or symptoms. Patients in
group 2 begin delayed ADT at least 2 years after study entry unless 1 of the following
clinical criteria is present: development of symptoms OR PSA ≥ 60 ng/mL OR PSA doubling time
of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart.

After 9 months of ADT, all patients are assessed for response. Patients with PSA < 4 ng/mL
may discontinue ADT. These patients are followed every 3 months. Treatment may be restarted
when PSA is > 20 ng/mL OR PSA is > the PSA level at study entry OR at clinical progression.

Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 3
years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
periodically thereafter at the discretion of the principal investigator.

PROJECTED ACCRUAL: A total of 300-2,000 patients will be accrued for this study within 2-5
years.