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

NCT00004001 | Completed Phase 3 DMC

• 3 other identifiers: CDR0000067211S9916U10CA032102
• Study Type: interventional
• Target: 770
• Locations: 1 country
• Sites: 16

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Compare overall survival in the two study arms

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

  up to 4 years

Secondary Outcomes (4)

• Compare progression-free survival between two study arms

  up to 4 years

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

  up to 4 years or time of disease progression

• Compare objective responses between two study arms

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

• Compare toxicities between the two study arms

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

Study Arms (2)

Docetaxel and Estramustine

EXPERIMENTAL

Estramustine, 280 mg, PO, TID, Days 1-5; q 21 days Docetaxel, 60mg/m2, IV, Day 2; q 21 days

Drug: docetaxel; Drug: estramustine

Mitoxantrone and Prednisone

ACTIVE COMPARATOR

Mitoxantrone, 12 mg/m2, IV, Day 1; q 21 days Prednisone, 5 mg, PO, BID, Days 1-21; q 21 days

Drug: mitoxantrone; Drug: prednisone

Interventions

docetaxel DRUG

Docetaxel and Estramustine

estramustine DRUG

Docetaxel and Estramustine

mitoxantrone DRUG

Mitoxantrone and Prednisone

prednisone DRUG

Mitoxantrone and Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator
• Cancer and Leukemia Group B: collaborator
• North Central Cancer Treatment Group: collaborator

Study Sites (16)

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, 85259-5404, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61602, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, 52403-1206, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309-1016, United States

Location

Siouxland Hematology-Oncology

Sioux City, Iowa, 51101-1733, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CentraCare Health Plaza

Saint Cloud, Minnesota, 56303, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Medcenter One Health System

Bismarck, North Dakota, 58501, United States

Location

CCOP - Merit Care Hospital

Fargo, North Dakota, 58122, United States

Location

Altru Health System

Grand Forks, North Dakota, 58201, United States

Location

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, 17822-2001, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57709, United States

Location

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, 57104, United States

Location

Related Publications (21)

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 19130298 RESULT

• 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.

  PMID: 16622120 RESULT

• 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.

  PMID: 16782921 RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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. doi: 10.1056/NEJMoa041318.

  PMID: 15470214 RESULT

• 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.

  PMID: 10604271 RESULT

• Unger JM, LeBlanc M, Blanke CD. The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population. JAMA Oncol. 2017 Oct 1;3(10):1345-1351. doi: 10.1001/jamaoncol.2017.0762.

  PMID: 28586789 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Estramustine; Mitoxantrone; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Quinones; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Daniel P. Petrylak, MD

  Herbert Irving Comprehensive Cancer Center

  STUDY CHAIR

• Eric J. Small, MD

  University of California, San Francisco

  STUDY CHAIR

• Patrick A. Burch, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: October 1, 1999
• Primary Completion: July 1, 2006
• Study Completion: January 1, 2007
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

US (16)