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

This study has been terminated.
(Permanently Closed Due to Safety Issue)
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00004124
First received: December 10, 1999
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: goserelin
Drug: mitoxantrone hydrochloride
Drug: prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: at month 4 and every 3 months for 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: at month 4 and every 3 months for 2 years ] [ Designated as safety issue: No ]
  • Qualitative and quantitative toxicity [ Time Frame: every 21 days for 4 months, then every 3 months for 2 years ] [ Designated as safety issue: Yes ]
  • Prostate-specific antigen (PSA) progression-free survival rate [ Time Frame: at month 4 and every 3 months for 2 years ] [ Designated as safety issue: No ]
  • Evaluation of biomarkers [ Time Frame: prestudy, weeks 24 and 28, and at progression ] [ Designated as safety issue: No ]

Enrollment: 983
Study Start Date: October 1999
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004124

  Show 234 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
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
  More Information

Publications:
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.

Additional 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, CALGB-99904, U10CA032102
Study First Received: December 10, 1999
Last Updated: October 3, 2012
Health Authority: United States: Federal Government

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
Androgens
Bicalutamide
Mitoxantrone
Prednisone
Goserelin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Glucocorticoids
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents
Androgen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on July 24, 2014