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Prostate CancerPhase 3NCT00004001

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

A Phase 3 study testing docetaxel, estramustine and mitoxantrone in people with Prostate Cancer, run by SWOG Cancer Research Network at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
docetaxel, estramustine and mitoxantrone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
770 participants
Where
16 sitesUnited States
Study dates
Oct 1999to Jan 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • Medcenter One Health System

    Bismarck, North Dakota, 58501

  • CCOP - Cedar Rapids Oncology Project

    Cedar Rapids, Iowa, 52403-1206

  • CCOP - Geisinger Clinic and Medical Center

    Danville, Pennsylvania, 17822-2001

  • CCOP - Iowa Oncology Research Association

    Des Moines, Iowa, 50309-1016

  • CCOP - Merit Care Hospital

    Fargo, North Dakota, 58122

  • Altru Health System

    Grand Forks, North Dakota, 58201

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • CCOP - Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • CCOP - Illinois Oncology Research Association

    Peoria, Illinois, 61602

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57709

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • CentraCare Health Plaza

    Saint Cloud, Minnesota, 56303

  • CCOP - Scottsdale Oncology Program

    Scottsdale, Arizona, 85259-5404

  • Siouxland Hematology-Oncology

    Sioux City, Iowa, 51101-1733

  • CCOP - Sioux Community Cancer Consortium

    Sioux Falls, South Dakota, 57104

  • CCOP - Carle Cancer Center

    Urbana, Illinois, 61801

Other trials in United States

About this study

Official title: Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer

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.

Read the 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.

Conditions
Prostate Cancer
Being tested
docetaxel, estramustine, mitoxantrone, prednisone
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00004001
Study groupRoleWhat they receive
Docetaxel and EstramustineExperimentalEstramustine, 280 mg, PO, TID, Days 1-5; q 21 days Docetaxel, 60mg/m2, IV, Day 2; q 21 days
Receives: Drug: docetaxel; Drug: estramustine
Mitoxantrone and PrednisoneActive comparatorMitoxantrone, 12 mg/m2, IV, Day 1; q 21 days Prednisone, 5 mg, PO, BID, Days 1-21; q 21 days
Receives: Drug: mitoxantrone; Drug: prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Compare overall survival in the two study arms

    Measured from date of registration to date of death due to any cause

    Measured: up to 4 years

Secondary outcomes (4)

  1. Compare progression-free survival between two study arms

    Measured from date of registration to date of first observation of progression disease, or death due to any cause

    Measured: up to 4 years

  2. Compare Prostate-Specific Antigen (PSA) response between two study arms

    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.

    Measured: up to 4 years or time of disease progression

  3. Compare objective responses between two study arms

    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.

    Measured: up to 12 cycles of treatment ( 1cycle = 21 days)

  4. Compare toxicities between the two study arms

    Measured: up to 12 cycles of treatment (1 cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startOct 1999
  3. Primary completionJul 2006
  4. Study completionJan 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
770 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004001
Sponsor's protocol ID
CDR0000067211
Other IDs
S9916, U10CA032102
Status last verified
Feb 2014
First submitted
1 Nov 1999
Last updated
25 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19380444

  • 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.

    PubMed 18307687

  • 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. doi: 10.1016/j.eururo.2006.08.013. Epub 2006 Aug 22.

    PubMed 17007996

  • 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.

    PubMed 17956560

  • 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.

    PubMed 17387372

  • 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.

    PubMed 17868721

  • 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.

    PubMed 16631461

  • 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.

    PubMed 17084173

  • 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.

    PubMed 16904054

  • 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.

    PubMed 16266195

  • 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 Mar;18(2):147-55. doi: 10.1007/s11136-008-9433-3. Epub 2009 Jan 9.

    PubMed 19130298

  • 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. doi: 10.1093/jnci/djj129.

    PubMed 16622120

  • 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. doi: 10.1200/JCO.2005.04.8207.

    PubMed 16782921

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing docetaxel, estramustine and mitoxantrone in people with Prostate Cancer, run by SWOG Cancer Research Network at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare overall survival in the two study arms (time frame: up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004001, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2014.

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