S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer|
- Compare overall survival in the two study arms [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]Measured from date of registration to date of death due to any cause
- Compare progression-free survival between two study arms [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]Measured from date of registration to date of first observation of progression disease, or death due to any cause
- Compare Prostate-Specific Antigen (PSA) response between two study arms [ Time Frame: up to 4 years or time of disease progression ] [ Designated as safety issue: No ]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.
- Compare objective responses between two study arms [ Time Frame: up to 12 cycles of treatment ( 1cycle = 21 days) ] [ Designated as safety issue: No ]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.
- Compare toxicities between the two study arms [ Time Frame: up to 12 cycles of treatment (1 cycle = 21 days) ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 1999|
|Study Completion Date:||January 2007|
|Primary Completion Date:||July 2006 (Final data collection date for primary outcome measure)|
Experimental: Docetaxel and Estramustine
Estramustine, 280 mg, PO, TID, Days 1-5; q 21 days Docetaxel, 60mg/m2, IV, Day 2; q 21 days
|Drug: docetaxel Drug: estramustine|
Active Comparator: Mitoxantrone and Prednisone
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|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004001
|United States, Arizona|
|CCOP - Scottsdale Oncology Program|
|Scottsdale, Arizona, United States, 85259-5404|
|United States, Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Illinois|
|CCOP - Illinois Oncology Research Association|
|Peoria, Illinois, United States, 61602|
|CCOP - Carle Cancer Center|
|Urbana, Illinois, United States, 61801|
|United States, Iowa|
|CCOP - Cedar Rapids Oncology Project|
|Cedar Rapids, Iowa, United States, 52403-1206|
|CCOP - Iowa Oncology Research Association|
|Des Moines, Iowa, United States, 50309-1016|
|Sioux City, Iowa, United States, 51101-1733|
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|CentraCare Health Plaza|
|Saint Cloud, Minnesota, United States, 56303|
|United States, Nebraska|
|CCOP - Missouri Valley Cancer Consortium|
|Omaha, Nebraska, United States, 68106|
|United States, North Dakota|
|Medcenter One Health System|
|Bismarck, North Dakota, United States, 58501|
|CCOP - Merit Care Hospital|
|Fargo, North Dakota, United States, 58122|
|Altru Health System|
|Grand Forks, North Dakota, United States, 58201|
|United States, Pennsylvania|
|CCOP - Geisinger Clinic and Medical Center|
|Danville, Pennsylvania, United States, 17822-2001|
|United States, South Dakota|
|Rapid City Regional Hospital|
|Rapid City, South Dakota, United States, 57709|
|CCOP - Sioux Community Cancer Consortium|
|Sioux Falls, South Dakota, United States, 57104|
|Study Chair:||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|