Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	MDA-DM-97022 NCI-T97-0023, NCT00003084, T97-0023

Objectives

I.  Determine the clinical benefit of two combination chemotherapy regimens, 
paclitaxel, etoposide, and estramustine vs ketoconazole, doxorubicin, 
vinblastine, and estramustine in patients with androgen independent prostate 
cancer, as measured by prostate specific antigen (PSA)-based response rate, 
time to progression, and overall survival.

II. Identify the most promising regimen to use in a phase III trial based on 
toxic effects, PSA-based response rates, and clinical benefit.

Entry Criteria

Disease Characteristics:

Histologically confirmed adenocarcinoma of the prostate

Androgen independent disease progression
 -Castrate testosterone level of less than 40 ng/dL (if medically achieved,   
  treatment must be maintained continuously)
 -Prostate specific antigen (PSA) at least 4 ng/mL and rising on at least 2   
  consecutive measurements

No variant histologies such as ductal carcinoma (endometrioid or cribiform) or
small cell carcinoma

Brain metastases controlled

Prior/Concurrent Therapy:

Biologic therapy:
 No prior ketoconazole

Chemotherapy:
 No prior doxorubicin, vinblastine, estramustine, paclitaxel, or etoposide
 No greater than one prior cytotoxic therapy
 No other concurrent chemotherapy
 At least 8 weeks since prior mitomycin 
 At least 60 days since prior suramin 

Endocrine therapy:
 No antiandrogen therapy such as flutamide or nilutamide within 4 weeks (6    
  weeks for bicalutamide) without response OR
 Progression since antiandrogen withdrawal
 Prior dexamethasone therapy discontinued

Radiotherapy:
 At least 10 weeks since prior strontium Sr 89 and no more than 1 prior
  regimen
 No concurrent strontium Sr 89

Surgery:
 Not specified

Other:
 No other concurrent therapy for prostate cancer
 No concurrent H2 blockers, omeprazole, or antacids
 No concurrent terfenadine and astemizole

Patient Characteristics:

Age:
 18 and over

Performance status:
 Zubrod 0-3

Life expectancy:
 At least 12 weeks

Hematopoietic:
 Absolute neutrophil count at least 1500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin greater than 9.5 g/dL (without transfusion support)

Hepatic:
 Bilirubin and transaminase less than 2 times the upper limit of normal

Renal:
 Creatinine no greater than 2.0 mg/dL OR
 Estimated creatinine clearance at least 35 mL/min

Cardiovascular:
 No clinical history of heart disease
 Normal ECG OR
 Ejection fraction (ECHO, MUGA, or ventriculography) at least 45%

Other:
 Spinal cord compression controlled
 No active peptic ulcer disease
 No active, or likely to become active, second malignancy

Expected Enrollment

A total of 92 patients (46 per treatment arm) will be accrued for this study.

Outline

This is a randomized multicenter study.  Patients are stratified according to 
risk group: low volume disease (no more than 2 lesions on bone scan), 
intermediate volume (more than 2 bone lesions confined to axial skeleton), or 
high volume (bone lesions in appendicular skeletal or visceral lesions).  
Patients are randomized to one of two treatment arms.

Arm I:  Patients receive oral estramustine three times a day and oral 
etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. 
Treatment repeats every 21 days.

Arm II:  Patients receive doxorubicin IV on days 1, 15, and 29, vinblastine IV 
on days 8, 22, and 36, oral ketoconazole three times a day on days 1-7, 15-21, 
and 29-35, and oral estramustine three times a day on days 8-14, 22-28, and 
36-42.  This regimen consists of 6 weeks of alternating chemotherapy and 2 
weeks rest, for an 8 week course.

Treatment continues in the absence of disease progression or unacceptable 
toxicity. 

Millikan R, Thall PF, Lee SJ, et al.: Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer. J Clin Oncol 21 (5): 878-83, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Randall Millikan, MD, PhD, Protocol chair		Ph: 713-563-7245; 800-392-1611 Email: rmillika@mdanderson.org

Registry Information
Official Title		A Randomized Phase II Trial of Taxol/VP-16/Estramustine vs. Ketoconazole/Doxorubicin/Vinblastine/Estramustine in Androgen Independent Prostate Cancer
Trial Start Date		1997-12-10
Registered in ClinicalTrials.gov		NCT00003084
Date Submitted to PDQ		1997-09-12
Information Last Verified		2007-05-14

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