Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI	SWOG-S9916 CLB-99808, NCCTG-S9916, NCT00004001, S9916

Special Category: CTSU trial

Objectives

1. 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.
2. Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
3. Compare the quality of life, including palliation of metastatic bone pain and global quality of life, of patients treated with these regimens.
4. Record prostate-specific antigen values for future correlations with response and survival in patients treated with these regimens.
5. Compare the responses in patients with bidimensionally measurable disease treated with these regimens.

Entry 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

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

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

Expected Enrollment

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

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.

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 18 (2): 147-55, 2009.[PUBMED Abstract]

Petrylak DP, Ankerst DP, Jiang CS, et al.: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst 98 (8): 516-21, 2006.[PUBMED Abstract]

Berry DL, Moinpour CM, Jiang CS, et al.: 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 24 (18): 2828-35, 2006.[PUBMED Abstract]

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, et al.: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351 (15): 1513-20, 2004.[PUBMED Abstract]

Hussain M, Petrylak D, Fisher E, et al.: 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 26 (5 Suppl 17): 55-60, 1999.[PUBMED Abstract]

Hussain M, Goldman B, Tangen C, et al.: Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916. J Clin Oncol 27 (15): 2450-6, 2009.[PUBMED Abstract]

de Wit R: Chemotherapy in hormone-refractory prostate cancer. BJU Int 101 (Suppl 2): 11-5, 2008.[PUBMED Abstract]

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.

Calabrò F, Sternberg CN: Current indications for chemotherapy in prostate cancer patients. Eur Urol 51 (1): 17-26, 2007.[PUBMED Abstract]

Chowdhury S, Burbridge S, Harper PG: Chemotherapy for the treatment of hormone-refractory prostate cancer. Int J Clin Pract 61 (12): 2064-70, 2007.[PUBMED Abstract]

Mendiratta P, Armstrong AJ, George DJ: Current standard and investigational approaches to the management of hormone-refractory prostate cancer. Rev Urol 9 (Suppl 1): S9-S19, 2007.[PUBMED Abstract]

Montgomery RB, Goldman B, Tangen CM, et al.: Association of body mass index with response and survival in men with metastatic prostate cancer: Southwest Oncology Group trials 8894 and 9916. J Urol 178 (5): 1946-51; discussion 1951, 2007.[PUBMED Abstract]

Burgess EF, Roth BJ: Changing perspectives of the role of chemotherapy in advanced prostate cancer. Urol Clin North Am 33 (2): 227-36, vii, 2006.[PUBMED Abstract]

Lucas A, Petrylak DP: The case for early chemotherapy for the treatment of metastatic disease. J Urol 176 (6 Pt 2): S72-5, 2006.[PUBMED Abstract]

Moss RA, Petrylak DP: Cytotoxic chemotherapy for prostate cancer: Who and when? Curr Treat Options Oncol 7 (5): 370-7, 2006.[PUBMED Abstract]

McKeage K, Keam SJ: Docetaxel in hormone-refractory metastatic prostate cancer. Drugs 65 (16): 2287-94; discussion 2295-7, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Daniel Petrylak, MD, Protocol chair		Ph: 212-305-1731 Email: dpp5@columbia.edu

Cancer and Leukemia Group B

Eric Small, MD, Protocol chair		Ph: 415-353-7095; 800-888-8664

North Central Cancer Treatment Group

Patrick Burch, MD, Protocol chair		Ph: 507-284-2511 Email: burch.patrick@mayo.edu

Registry Information
Official Title		Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer
Trial Start Date		1999-10-15
Trial Completion Date		2006-07-01
Registered in ClinicalTrials.gov		NCT00004001
Date Submitted to PDQ		1999-07-22
Information Last Verified		2003-05-14
NCI Grant/Contract Number		CA32102

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