Official Title: “Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination With Hormone Therapy in Patients With High-Risk Metastic Adenocarinoma of the Prostate”

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining chemotherapy with hormone therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus hormone therapy in treating patients who have metastatic prostate cancer.

Study Type: Interventional

Study Design: Treatment, Open Label

OBJECTIVES: - Determine the progression-free and overall survival in patients with high-risk metastatic adenocarcinoma of the prostate treated with early estramustine, etoposide, and paclitaxel with combined androgen-blockade therapy. - Determine the type, frequency, and severity of toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study. - Androgen-blockade therapy: Patients receive a standard regimen of luteinizing hormone-releasing hormone agonist therapy comprising either goserelin subcutaneously once monthly or once every 3 months or leuprolide intramuscularly once monthly, once every 3 months, or once every 4 months. Patients also receive a standard regimen of antiandrogen therapy comprising oral bicalutamide, oral flutamide, or oral nilutamide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. - Chemotherapy: Beginning 14-30 days after initiation of androgen-blockade therapy, patients receive oral estramustine three times daily and oral etoposide once daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 2 years.

Intervention(s) in this Clinical Trial

• Drug: bicalutamide
• Drug: estramustine phosphate sodium
• Drug: etoposide
• Drug: flutamide
• Drug: goserelin
• Drug: leuprolide acetate
• Drug: nilutamide
• Drug: paclitaxel

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed high-risk adenocarcinoma of the prostate
• Clinical stage D2 disease as evidenced by one of the following:
• Visceral disease (liver, lung, or other viscera)
• Bone metastases to sites in both the axial (spine, pelvis, ribs, or skull) and appendicular (claviculae, humeri, or femora) skeleton
• No prior or concurrent (treated or untreated) brain metastases
• Patients with clinical evidence of brain metastasis must have a negative brain CT or MRI
• No evidence of untreated spinal cord compression

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No active hypercoagulability

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No transient ischemic attacks, stroke, or myocardial infarction within the past 6 months
• No active coronary artery disease requiring antianginal therapy
• No active thrombophlebitis

Pulmonary:

• No history of pulmonary embolus

Other:

• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated 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 concurrent biologic therapy

Chemotherapy:

• No prior cytotoxic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Prior androgen-blockade therapy (e.g., luteinizing hormone-releasing hormone agonist and antiandrogen therapy) allowed if administered for a duration of less than 30 days
• Prior neoadjuvant hormonal therapy allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• At least 4 weeks since prior surgery and recovered

Other:

• No concurrent bisphosphonates

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Southwest Oncology Group

Overall Clinical Trial Officials and Contacts

David C. Smith, MD Study Chair University of Michigan Cancer Center  

Information obtained from ClinicalTrials.gov on January 06, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00028769

Study ID Number: CDR0000069132

ClinicalTrials.gov Identifier: NCT00028769

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database