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Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy
This study has been completed.
Sponsors and Collaborators: Southwest Oncology Group
National Cancer Institute (NCI)
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004001
  Purpose

RATIONALE: Drugs used in chemotherapy and hormone therapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. It is not yet known whether estramustine plus docetaxel is more effective than mitoxantrone plus prednisone for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of estramustine plus docetaxel with that of mitoxantrone plus prednisone in treating patients who have stage IV prostate cancer that has not responded to hormone therapy.


Condition Intervention Phase
Prostate Cancer
Drug: docetaxel
Drug: estramustine phosphate sodium
Drug: mitoxantrone hydrochloride
Drug: prednisone
Phase III

MedlinePlus related topics: Cancer Prostate Cancer
Drug Information available for: Docetaxel Mitoxantrone hydrochloride Mitoxantrone Prednisone Estramustine Estramustine phosphate Estramustine phosphate sodium
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 620
Study Start Date: October 1999
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the overall survival and progression-free survival in patients with hormone-refractory, metastatic adenocarcinoma of the prostate treated with docetaxel and estramustine vs mitoxantrone and prednisone.
  • Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
  • Compare the quality of life, including palliation of metastatic bone pain and global quality of life, of patients treated with these regimens.
  • Record prostate-specific antigen values for future correlations with response and survival in patients treated with these regimens.
  • Compare the responses in patients with bidimensionally measurable disease treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease status (measurable or evaluable disease progression vs rising PSA only), NCI Common Toxicity Criteria version 2.X pain scale (grade 2 or greater vs less than 2), and SWOG performance status (0-1 vs 2-3). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour on day 2.
  • Arm II: Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21.

Treatment in both arms repeats every 3 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, after courses 4 and 8, and then at 1 year after randomization.

Patients are followed every 6 months for 2 years and then annually for 1 year.

PROJECTED ACCRUAL: A total of 620 patients (310 per arm) will be accrued for this study within 3.5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic adenocarcinoma of the prostate
  • Unresponsive or refractory to hormonal therapy, as defined by at least 1 of the following criteria:

    • Progression of bidimensionally measurable disease
    • Progression of evaluable but not measurable disease (bone scan)
    • At least 2 consecutive rises in PSA and a PSA level of at least 5 ng/mL
  • No minimum PSA required for measurable disease or non-PSA evaluable disease
  • Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease
  • Prior orchiectomy OR
  • Medical castration using leuprolide or goserelin

    • LHRH agonist therapy must continue during study
  • Prior nonsteroidal antiandrogens (flutamide, ketoconazole, bicalutamide, or nilutamide) allowed if disease progression occurred
  • No third-space fluid accumulation such as ascites or symptomatic pleural effusion
  • No brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • SWOG 0-3
  • Performance status 3 must be due to pain secondary to bone metastases

Life expectancy:

  • Not specified

Hematopoietic:

  • No hypercoagulability

Hepatic:

  • Not specified

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No history of myocardial infarction
  • No history of congestive heart failure unless well controlled
  • No history of cerebrovascular accident or atrial fibrillation
  • No active thrombophlebitis
  • LVEF at least 50% by MUGA scan or 2-D echocardiogram

Pulmonary:

  • No history of pulmonary embolus

Other:

  • Recovered from major infections
  • No other significant active medical illness
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy and recovered
  • No more than 1 prior biologic therapy regimen
  • No concurrent biological response modifiers

Chemotherapy:

  • At least 4 weeks since prior chemotherapy and recovered
  • No more than 1 prior chemotherapy regimen
  • No prior estramustine, taxanes, anthracyclines, or mitoxantrone
  • No other concurrent chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • At least 4 weeks since prior flutamide or ketoconazole (6 weeks for bicalutamide or nilutamide)
  • No concurrent corticosteroids or hormonal therapy (except megestrol for hot flashes or continuing LHRH treatment)

Radiotherapy:

  • See Disease Characteristics
  • Prior samarium Sm 153 lexidronam pentasodium allowed
  • At least 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to 30% or more of bone marrow
  • No prior strontium chloride Sr 89
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics
  • At least 3 weeks since prior surgery and recovered

Other:

  • At least 4 weeks since prior bisphosphonates
  • No prior anticoagulation therapy (i.e., warfarin), except aspirin
  • No concurrent bisphosphonates
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004001

Locations
United States, Arizona
CCOP - Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Minnesota
CentraCare Health Plaza
Saint Cloud, Minnesota, United States, 56303
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
Altru Health System
Grand Forks, North Dakota, United States, 58201
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Medcenter One Health System
Bismarck, North Dakota, United States, 58501
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Investigators
Study Chair: Daniel P. Petrylak, MD Herbert Irving Comprehensive Cancer Center
Study Chair: Eric J. Small, MD UCSF Helen Diller Family Comprehensive Cancer Center
Study Chair: Patrick A. Burch, MD Mayo Clinic
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Moinpour CM, Donaldson GW, Nakamura Y. Chemotherapeutic impact on pain and global health-related quality of life in hormone-refractory prostate cancer: Dynamically Modified Outcomes (DYNAMO) analysis of a randomized controlled trial. Qual Life Res. 2009 Jan 9; [Epub ahead of print]
Petrylak DP, Ankerst DP, Jiang CS, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst. 2006 Apr 19;98(8):516-21.
Southwest Oncology Group; Berry DL, Moinpour CM, Jiang CS, Ankerst DP, Petrylak DP, Vinson LV, Lara PN, Jones S, Taplin ME, Burch PA, Hussain MH, Crawford ED. Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol. 2006 Jun 20;24(18):2828-35.
Berry DL, Moinpour CM, Jiang C, et al.: Quality of life (QOL) and pain in advanced stage prostate cancer: impact of missing data on evaluating palliation in SWOG 9916. [Abstract] J Clin Oncol 22 (Suppl 14): A-4579, 401s, 2004.
Crawford ED, Pauler DK, Tangen CM, et al.: Three-month change in PSA as a surrogate endpoint for mortality in advanced hormone-refractory prostate cancer (HRPC): data from Southwest Oncology Group study S9916. [Abstract] J Clin Oncol 22 (Suppl 14): A-4505, 383s, 2004.
Petrylak DP, Tangen C, Hussain M, et al.: SWOG 99-16: randomized phase III trial of docetaxel (D)/estramustine (E) versus mitoxantrone(M)/prednisone(p) in men with androgen-independent prostate cancer (AIPCA). [Abstract] J Clin Oncol 22 (Suppl 14): A-3, 2s, 2004.
Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20.
Hussain M, Petrylak D, Fisher E, Tangen C, Crawford D. Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Semin Oncol. 1999 Oct;26(5 Suppl 17):55-60.

Other Publications:
de Wit R. Chemotherapy in hormone-refractory prostate cancer. BJU Int. 2008 Mar;101 Suppl 2:11-5.
Goldman B, Hussain M, Tangen C, et al.: Prostate-specific antigen progression (PSA-P) as a predictor of overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-165, 2008.
Hussain MH, Goldman B, Tangen CM, et al.: Use of prostate-specific antigen progression (PSA-P) to predict overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] J Clin Oncol 26 (Suppl 15): A-5015, 2008.
Calabro F, Sternberg CN. Current indications for chemotherapy in prostate cancer patients. Eur Urol. 2007 Jan;51(1):17-26. Epub 2006 Aug 22.
Chowdhury S, Burbridge S, Harper PG. Chemotherapy for the treatment of hormone-refractory prostate cancer. Int J Clin Pract. 2007 Dec;61(12):2064-70. Epub 2007 Oct 23.
Mendiratta P, Armstrong AJ, George DJ. Current standard and investigational approaches to the management of hormone-refractory prostate cancer. Rev Urol. 2007;9 Suppl 1:S9-S19.
Montgomery RB, Goldman B, Tangen CM, Hussain M, Petrylak DP, Page S, Klein EA, Crawford ED. Association of Body Mass Index With Response and Survival in Men With Metastatic Prostate Cancer: Southwest Oncology Group Trials 8894 and 9916. J Urol. 2007 Sep 12; [Epub ahead of print]
Burgess EF, Roth BJ. Changing perspectives of the role of chemotherapy in advanced prostate cancer. Urol Clin North Am. 2006 May;33(2):227-36, vii. Review.
Lucas A, Petrylak DP. The case for early chemotherapy for the treatment of metastatic disease. J Urol. 2006 Dec;176(6 Pt 2):S72-5. Review.
Moss RA, Petrylak DP. Cytotoxic chemotherapy for prostate cancer: Who and when? Curr Treat Options Oncol. 2006 Sep;7(5):370-7. Review.
McKeage K, Keam SJ. Docetaxel in hormone-refractory metastatic prostate cancer. Drugs. 2005;65(16):2287-94; discussion 2295-7. Review.

Study ID Numbers: CDR0000067211, SWOG-S9916, CLB-99808, NCCTG-S9916
Study First Received: November 1, 1999
Last Updated: January 28, 2009
ClinicalTrials.gov Identifier: NCT00004001  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer

Study placed in the following topic categories:
Docetaxel
Prednisone
Prostatic Diseases
Genital Neoplasms, Male
Estramustine
Urogenital Neoplasms
Mitoxantrone
Genital Diseases, Male
Adenocarcinoma
Prostatic Neoplasms
Recurrence

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Glucocorticoids
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Sensory System Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 30, 2009