SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: goserelin acetate; Drug: bicalutamide; Other: clinical observation

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00002651

CAN-NCIC-PR8

CAN-NCIC-JPR8

CALGB-9594

INT-0162

CDR0000064184

SWOG-9346

ECOG-S9346

EORTC-30985

Details and patient eligibility

About

RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy may be effective treatment for prostate cancer. It is not yet known which regimen of hormone therapy is most effective for stage IV prostate cancer.

PURPOSE: This randomized phase III trial is studying two different regimens of hormone therapy and comparing how well they work in treating men with stage IV prostate cancer.

Full description

OBJECTIVES:

Primary

• Compare the survival of patients with metastatic stage IV prostate cancer responsive to combined androgen-deprivation therapy (CAD) treated with intermittent vs continuous CAD.
• Compare the effects of these treatment regimens on impotence, libido, and vitality/fatigue as well as the physical and emotional well-being of these patients.

Secondary

• Compare general symptoms, role functioning, global perception of quality of life, and social functioning of patients treated with these regimens.
• Assess prostate-specific antigen (PSA) levels after continuous CAD administered before randomization and evaluate PSA changes throughout randomized treatment of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to SWOG performance status (0-1 vs 2), severity of disease (minimal vs extensive), and prior hormonal therapy (neoadjuvant hormonal therapy vs finasteride vs neither).

• Induction therapy: Patients receive combined androgen-deprivation (CAD) therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily for 8 courses (7 months).

• Consolidation therapy: Patients are randomized to 1 of 2 consolidation regimens.

  • Arm I (continuous CAD therapy): Patients continue CAD therapy as in induction therapy. Treatment continues in the absence of disease progression.
  • Arm II (intermittent CAD therapy): Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in induction therapy. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.

Quality of life is assessed before induction therapy, at 3 months (before consolidation therapy), and then at 9 and 15 months.

Patients are followed every 6-12 months for at least 10 years.

PROJECTED ACCRUAL: Approximately 1,500 patients will be accrued for this study.

Enrollment: 3,040 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

  • Metastatic stage IV (stage D2)

    • Any number of bone metastases by bone scan allowed
    • Unequivocal visceral organ metastases (liver, brain, or lung) allowed

  • No suspected second primary tumors unless metastases are histologically confirmed, including special stains (e.g., prostate specific antigen [PSA] and prostatic alkaline phosphatase [PAP])

• For entry into late induction therapy:

  • No more than 1 month from the beginning of antiandrogen therapy to the beginning of luteinizing hormone-releasing hormone (LHRH) agonist therapy
  • No more than 6 months since initiation of current combined androgen-deprivation therapy (LHRH agonist and antiandrogen)
  • The effectiveness of the current depot LHRH agonist would not extend beyond 8 months after initiation of combined androgen therapy

• PSA at least 5 ng/mL

• No acute spinal cord compression

PATIENT CHARACTERISTICS:

Age:

• Adult

Performance status:

• SWOG 0-2

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Recovered from any major infection

• No active medical illness that would preclude study or limit survival

• No other malignancy within the past 5 years except:

  • Adequately treated basal cell or squamous cell skin cancer
  • Adequately treated carcinoma in situ of the bladder
  • Adequately treated other superficial cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biological response modifier therapy

Chemotherapy:

• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics

• More than 1 year since any prior neoadjuvant or adjuvant hormonal therapy for a duration of no more than 4 months

  • Single or combination therapy allowed

• More than 1 year since prior finasteride for prostate cancer for a duration of no more than 9 months (less than 6 months for benign prostatic hypertrophy)

• Prior or concurrent megestrol for hot flashes allowed

• No other concurrent hormonal therapy

Radiotherapy:

• No concurrent radiotherapy other than palliation of painful bone metastases

Surgery:

• No prior bilateral orchiectomy
• Recovered from any prior major surgery

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,040 participants in 2 patient groups

Consolidation arm I

Active Comparator group

Description:

Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression.

Treatment:

Drug: bicalutamide

Drug: goserelin acetate

Consolidation arm II

Experimental group

Description:

Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.

Treatment:

Drug: bicalutamide

Drug: goserelin acetate

Other: clinical observation