Clinical trial NCT00004001: S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy
Official title: Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Cancer and Leukemia Group B
name: North Central Cancer Treatment Group
First posted: 2003-01-27
Enrollment: 770
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Compare overall survival in the two study arms
timeFrame: up to 4 years
Secondary outcomes:
measure: Compare progression-free survival between two study arms
timeFrame: up to 4 years
measure: Compare Prostate-Specific Antigen (PSA) response between two study arms
timeFrame: up to 4 years or time of disease progression
measure: Compare objective responses between two study arms
timeFrame: up to 12 cycles of treatment ( 1cycle = 21 days)
measure: Compare toxicities between the two study arms
timeFrame: up to 12 cycles of treatment (1 cycle = 21 days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Health Plaza
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Health System
state: North Dakota
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: Daniel P. Petrylak, MD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Eric J. Small, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Patrick A. Burch, MD
role: STUDY_CHAIR
References:
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