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

NCT ID: NCT00004001

Last Updated: 2014-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 770 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-10-31
• Study Completion Date: 2007-01-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel and Estramustine

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

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

estramustine

Intervention Type: DRUG

Mitoxantrone and Prednisone

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

Group Type: ACTIVE_COMPARATOR

mitoxantrone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

Interventions

docetaxel

Intervention Type: DRUG

estramustine

Intervention Type: DRUG

mitoxantrone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel P. Petrylak, MD

Role: STUDY_CHAIR

Herbert Irving Comprehensive Cancer Center

Eric J. Small, MD

Role: STUDY_CHAIR

University of California, San Francisco

Patrick A. Burch, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CentraCare Health Plaza

Saint Cloud, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Altru Health System

Grand Forks, North Dakota, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: RESULT

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Other Identifiers

S9916

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067211

Identifier Type: -

Identifier Source: org_study_id