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

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ClinicalTrials.gov Identifier: NCT00004124
Recruitment Status : Active, not recruiting
First Posted : January 27, 2003
Results First Posted : September 3, 2018
Last Update Posted : September 3, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: bicalutamide Drug: goserelin Drug: mitoxantrone hydrochloride Drug: prednisone Phase 3

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 983 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation in Selected High-Risk Prostate Cancer Patients Following Radical Prostatectomy
Study Start Date : October 1999
Actual Primary Completion Date : June 2017
Estimated Study Completion Date : June 1, 2022


Arm Intervention/treatment
Active Comparator: bicalutamide, goserelin
androgen deprivation
Drug: bicalutamide
Other Name: Casodex

Drug: goserelin
Other Name: Zoladex

Experimental: bicalutamide, goserelin, mitoxantrone, prednisone
androgen deprivation plus mitoxantrone, prednisone
Drug: bicalutamide
Other Name: Casodex

Drug: goserelin
Other Name: Zoladex

Drug: mitoxantrone hydrochloride
Drug: prednisone



Primary Outcome Measures :
  1. Overall Survival [ Time Frame: at 10 Years ]
    Measured from date of randomization to date of death from any cause. Patient known to be alive are censored at date of last contact.

  2. Disease Free Survival [ Time Frame: at 10 Years ]
    Measured from date of randomization to date of first observation of recurrence or death due to any cause. Patients without recurrence are censored at date of last contact.


Secondary Outcome Measures :
  1. Compare Qualitative and Quantitative Toxicities of These Regimens in These Patients [ Time Frame: Up to 22 months from registration ]
    Number of patients with adverse events that are related to study drug

  2. PSA Progression Free Survival [ Time Frame: Up to 10 Years ]
    Measured from date of randomization to date of PSA progression or death due to any cause. PSA progression is defined as a serum PSA level of > 0.2 ng/mL measured on 3 consecutive occasions or in the absence of increasing PSA, a positive bone scan result or other radiographic or histologic evidence of progression will be used. Date of progression will be the date that the first measure of increasing PSA is noted in the series of 3.

  3. PSA Progression as Surrogate Endpoint for Overall Survival or Disease Free Survival [ Time Frame: Up to 10 Years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004124


  Show 234 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Investigators
Study Chair: L. Michael Glode, MD University of Colorado, Denver
Study Chair: Nancy A. Dawson, MD University of Maryland Greenebaum Cancer Center
  Study Documents (Full-Text)

Documents provided by Southwest Oncology Group:

Publications of Results:
Glode LM, Tangen CM, Hussain MH, et al.: Southwest Oncology Group S9921: prolonged event-free survival in high-risk prostate cancer (PC) patients receiving adjuvant androgen deprivation. [Abstract] J Clin Oncol 27 (Suppl 15): A-5009, 2009.
Glode LM, Hussain MH, Benson MC, et al.: SWOG 9921: a phase III multi-institutional trial of adjuvant therapy for high risk prostate cancer after radical prostatectomy. [Abstract] American Society of Clinical Oncology 2007 Prostate Cancer Symposium, 22-24 February 2007, Orlando, FL. A-349, 2007.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00004124     History of Changes
Other Study ID Numbers: CDR0000067352
S9921 ( Other Identifier: SWOG )
CALGB-99904 ( Other Identifier: CALGB )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: September 3, 2018
Last Update Posted: September 3, 2018
Last Verified: August 2018

Keywords provided by Southwest Oncology Group:
adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Goserelin
Bicalutamide
Mitoxantrone
Androgens
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Androgen Antagonists
Hormone Antagonists