NCT00004001 · CITED IN SOURCE DOCUMENTS

S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2014-02-25

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility 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 * Luteinizing hormone-releasing hormone (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 * Left ventricular ejection fraction (LVEF) at least 50% by Multi Gated Acquisition Scan (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
healthy Volunteers: false
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Estramustine, 280 mg, PO, TID, Days 1-5; q 21 days Docetaxel, 60mg/m2, IV, Day 2; q 21 days
intervention Names
Drug: docetaxel
Drug: estramustine
label
Docetaxel and Estramustine
type
EXPERIMENTAL
description
Mitoxantrone, 12 mg/m2, IV, Day 1; q 21 days Prednisone, 5 mg, PO, BID, Days 1-21; q 21 days
intervention Names
Drug: mitoxantrone
Drug: prednisone
label
Mitoxantrone and Prednisone
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Docetaxel and Estramustine
name
docetaxel
type
DRUG
arm Group Labels
Docetaxel and Estramustine
name
estramustine
type
DRUG
arm Group Labels
Mitoxantrone and Prednisone
name
mitoxantrone
type
DRUG
arm Group Labels
Mitoxantrone and Prednisone
name
prednisone
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 770
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Measured from date of registration to date of death due to any cause
measure
Compare overall survival in the two study arms
time Frame
up to 4 years

secondary Outcomes

description
Measured from date of registration to date of first observation of progression disease, or death due to any cause
measure
Compare progression-free survival between two study arms
time Frame
up to 4 years
description
A confirmed partial response of non-measurable disease was defined as a reduction by more than 50% over baseline in two or more Prostate-Specific Antigen (PSA) measurements obtained at least four weeks apart, with no evidence of disease progression on imaging. Progressive disease was defined as a 25% increase in the serum PSA level - to at least 5 ng per milliliter - over the last preregistration measurement, with confirmation of the increase at least four weeks later. For patients with a decrease in serum PSA levels during the trial, progressive disease was defined as a confirmed increase of 25%, to at least 5 ng per milliliter over the nadir.
measure
Compare Prostate-Specific Antigen (PSA) response between two study arms
time Frame
up to 4 years or time of disease progression
description
Objective responses were defined on the basis of the sum of bi-dimensional measurements of metastatic lesions. Confirmed objective responses required a follow-up scan (a minimum of four weeks later) that demonstrated a continued response. Progression was defined by one of the following: a 50 percent increase or an increase of 10 cm\^2, whichever was smaller, in the sum of measurements of metastatic lesions over the sum at baseline; a clear worsening of nonmeasurable disease; reappearance of any lesion that had disappeared; appearance of any new lesion; or death.
measure
Compare objective responses between two study arms
time Frame
up to 12 cycles of treatment ( 1cycle = 21 days)
measure
Compare toxicities between the two study arms
time Frame
up to 12 cycles of treatment (1 cycle = 21 days)

Full study description

brief Summary: 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.
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.

Source references

references

citation
Hussain M, Goldman B, Tangen C, Higano CS, Petrylak DP, Wilding G, Akdas AM, Small EJ, Donnelly BJ, Sundram SK, Burch PA, Dipaola RS, Crawford ED. 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. 2009 May 20;27(15):2450-6. doi: 10.1200/JCO.2008.19.9810. Epub 2009 Apr 20.
pmid
19380444
type
BACKGROUND
citation
de Wit R. Chemotherapy in hormone-refractory prostate cancer. BJU Int. 2008 Mar;101 Suppl 2:11-5. doi: 10.1111/j.1464-410X.2007.07485.x.
pmid
18307687
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
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.
type
BACKGROUND
citation
Calabro F, Sternberg CN. Current indications for chemotherapy in prostate cancer patients. Eur Urol. 2007 Jan;51(1):17-26. doi: 10.1016/j.eururo.2006.08.013. Epub 2006 Aug 22.
pmid
17007996
type
BACKGROUND
citation
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. doi: 10.1111/j.1742-1241.2007.01551.x. Epub 2007 Oct 23.
pmid
17956560
type
BACKGROUND
citation
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(Suppl 1):S9-S19.
pmid
17387372
type
BACKGROUND
citation
Montgomery RB, Goldman B, Tangen CM, Hussain M, Petrylak DP, Page S, Klein EA, Crawford ED; Southwest Oncology Group. 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 Nov;178(5):1946-51; discussion 1951. doi: 10.1016/j.juro.2007.07.026. Epub 2007 Sep 17.
pmid
17868721
type
BACKGROUND
citation
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. doi: 10.1016/j.ucl.2005.12.006.
pmid
16631461
type
BACKGROUND
citation
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. doi: 10.1016/j.juro.2006.06.077.
pmid
17084173
type
BACKGROUND
citation
Moss RA, Petrylak DP. Cytotoxic chemotherapy for prostate cancer: Who and when? Curr Treat Options Oncol. 2006 Sep;7(5):370-7. doi: 10.1007/s11864-006-0005-x.
pmid
16904054
type
BACKGROUND
citation
McKeage K, Keam SJ. Docetaxel in hormone-refractory metastatic prostate cancer. Drugs. 2005;65(16):2287-94; discussion 2295-7. doi: 10.2165/00003495-200565160-00003.
pmid
16266195
type
BACKGROUND

Source notices and limitations

Discovery and provenance

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ry or radiation therapy.[<a href="#cit/section_1.54">54</a>]</p> <p id="_2111" tabindex="-1">Likewise, a retrospective analysis (<a href="/clinicaltrials/NCT00004001">SWOG-S9916</a> [NCT00004001]) showed PSA declines of 20% to 40% (but not 50%) at 3 months and 30% or more at 2 months after initiation of chemotherapy for ho
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ref="#cit/section_1.54">54</a>]</p> <p id="_2111" tabindex="-1">Likewise, a retrospective analysis (<a href="/clinicaltrials/NCT00004001">SWOG-S9916</a> [NCT00004001]) showed PSA declines of 20% to 40% (but not 50%) at 3 months and 30% or more at 2 months after initiation of chemotherapy for hormone-independent prostate ca
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Prostate Cancer Treatment (PDQ®)–Health Professional Version
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Updated: May 14, 2025
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May 14, 2025
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Preserved source evidence · Not medical advice