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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004001
• Other study ID #: CDR0000067211
• Secondary ID: S9916U10CA032102
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: February 21, 2014
• Start date: October 1999
• Est. completion date: January 2007

Study information

• Verified date: February 2014
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 770
• Est. completion date: January 2007
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel

• estramustine

• mitoxantrone

• prednisone

Locations

Country	Name	City	State
United States	Medcenter One Health System	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Altru Health System	Grand Forks	North Dakota
United States	Mayo Clinic	Jacksonville	Florida
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CentraCare Health Plaza	Saint Cloud	Minnesota
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Carle Cancer Center	Urbana	Illinois

Sponsors (4)

Lead Sponsor	Collaborator
Southwest Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI), North Central Cancer Treatment Group

Country where clinical trial is conducted

United States, 

References & Publications (20)

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.

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. — View Citation

Calabrò F, Sternberg CN. Current indications for chemotherapy in prostate cancer patients. Eur Urol. 2007 Jan;51(1):17-26. Epub 2006 Aug 22. Review. — View 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. Epub 2007 Oct 23. Review. — View Citation

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

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. Review. — View 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.

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. — View Citation

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 O — View 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.

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. — View Citation

McKeage K, Keam SJ. Docetaxel in hormone-refractory metastatic prostate cancer. Drugs. 2005;65(16):2287-94; discussion 2295-7. Review. — View 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:S9-S19. — View Citation

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 M — View 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. Epub 2007 Sep 17. — View Citation

Moss RA, Petrylak DP. Cytotoxic chemotherapy for prostate cancer: Who and when? Curr Treat Options Oncol. 2006 Sep;7(5):370-7. Review. — View Citation

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 — View Citation

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, 2

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 prostat — View Citation

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 Grou — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	up to 4 years	No
Secondary	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.	up to 4 years or time of disease progression	No
Secondary	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.	up to 12 cycles of treatment ( 1cycle = 21 days)	No
Secondary	Compare toxicities between the two study arms		up to 12 cycles of treatment (1 cycle = 21 days)	Yes