S9921, Hormone Therapy With or Without Mitoxantrone and Prednisone in Patients Who Have Undergone Radical Prostatectomy for Prostate Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: goserelin; Drug: mitoxantrone hydrochloride; Drug: prednisone; Drug: bicalutamide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00004124

CDR0000067352

U10CA032102 (U.S. NIH Grant/Contract)

CALGB-99904 (Other Identifier)

S9921 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus mitoxantrone and prednisone is more effective than hormone therapy alone for prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy, mitoxantrone, and prednisone to see how well they work compared to hormone therapy alone in treating patients who have undergone radical prostatectomy for prostate cancer.

Full description

OBJECTIVES:

• Compare the overall and disease-free survival of patients with high-risk adenocarcinoma of the prostate treated with adjuvant androgen deprivation therapy with or without mitoxantrone and prednisone after radical prostatectomy.
• Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
• Compare the prostate-specific antigen (PSA) progression-free survival rate in patient treated with these regimens.
• Determine whether PSA progression is a surrogate endpoint for survival or disease-free survival in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to surgical extent of disease (organ confined vs not organ confined, but N0 vs N1), Gleason's sum (less than 7 vs 7 vs greater than 7), and planned radiotherapy (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I:Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.
• Arm II:Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.

Patients may undergo radiotherapy 5 days a week for 6.5-7.8 weeks beginning anytime (arm I) or after completion of chemotherapy (arm II), at the discretion of the physician, in the absence of disease progression or unacceptable toxicity.

Patients are offered the possibility to participate in biomarker research by allowing their tissue/blood to be studied.

Patients are followed every 6 months for 2 years and then annually for up to 13 years.

PROJECTED ACCRUAL: A total of 1,360 patients (680 per treatment arm) will be accrued for this study within 9.5 years.

Enrollment: 983 patients

Sex: Male

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage T1-T3 adenocarcinoma of the prostate before radical prostatectomy and lymph node dissection

  • Must have undergone prostatectomy within the past 120 days

• Must meet at least 1 of the following pathologic criteria:

  • Gleason sum at least 8
  • pT3b (seminal vesicle), pT4, or N1
  • Gleason sum of 7 and positive margin
  • Preoperative PSA greater than 15 ng/mL, Gleason score greater than 7, or PSA level greater than 10 ng/mL and Gleason score greater than 6

• Must have an undetectable PSA (no greater than 0.2 ng/mL) documented after surgery or prior to adjuvant hormonal therapy (for patients initiating adjuvant hormonal therapy prior to study)

• No evidence of metastatic disease on bone scan if PSA is 20 ng/mL or greater at clinical diagnosis

• No distant metastatic disease

PATIENT CHARACTERISTICS:

Performance status:

• SWOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No uncontrolled congestive heart failure
• If history of cardiac disease, LVEF at least 50% by MUGA scan or 2-D echocardiogram

Other:

• No HIV positivity
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Prior neoadjuvant hormonal therapy of no more than 4 months duration before radical prostatectomy allowed
• Other concurrent adjuvant hormonal therapy allowed if initiated prior to study
• Concurrent low-dose megestrol (less than 40 mg/day) for hot flashes allowed

Radiotherapy:

• No prior radiotherapy
• No concurrent whole pelvis irradiation
• Concurrent radiotherapy allowed at the discretion of the physician

Surgery:

• See Disease Characteristics
• See Endocrine therapy
• Recovered from prior surgery

Other:

• No other prior or concurrent therapy for adenocarcinoma of the prostate

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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983 participants in 2 patient groups

bicalutamide, goserelin

Active Comparator group

Description:

androgen deprivation

Treatment:

Drug: bicalutamide

Drug: goserelin

bicalutamide, goserelin, mitoxantrone, prednisone

Experimental group

Description:

androgen deprivation plus mitoxantrone, prednisone

Treatment:

Drug: bicalutamide

Drug: prednisone

Drug: goserelin

Drug: mitoxantrone hydrochloride