search
Back to results

Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Doxorubicin Hydrochloride
Estramustine phosphate sodium
Etoposide
Ketoconazole
Paclitaxel
Vinblastine
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer, Chemotherapy, Ketoconazole, Estramustine, Etoposide, Paclitaxel, Doxorubicin, Vinblastine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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 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 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

Sites / Locations

  • University of Texas - MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (Estramustine + Etoposide)

Arm II (Chemotherapy + Ketoconazole)

Arm Description

Arm I: Oral Estramustine 3 x day + oral Etoposide 2 x day on days 1-14 + Paclitaxel IV over 1 hour Day 2, repeats every 21 days.

Arm II: Doxorubicin IV Days 1, 15, and 29, Vinblastine IV Days 8, 22, and 36, Oral Ketoconazole 3 x day on Days 1-7, 15-21, + 29-35, and Oral Estramustine 3 x day on Days 8-14, 22-28, and 36-42; 6 weeks of alternating chemotherapy and 2 weeks rest, for 8 week course.

Outcomes

Primary Outcome Measures

Prostate specific antigen (PSA)- based Response Rate

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
July 27, 2012
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00003084
Brief Title
Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer
Official Title
A Randomized Phase II Trial of Taxol/VP-16/Estramustine vs. Ketoconazole/Doxorubicin/Vinblastine/Estramustine in Androgen Independent Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
December 1997 (undefined)
Primary Completion Date
November 2002 (Actual)
Study Completion Date
November 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy consisting of paclitaxel, etoposide, and estramustine as compared with ketoconazole plus doxorubicin, vinblastine, and estramustine in treating patients with prostate cancer.
Detailed Description
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. 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. PROJECTED ACCRUAL: A total of 92 patients (46 per treatment arm) will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer, Chemotherapy, Ketoconazole, Estramustine, Etoposide, Paclitaxel, Doxorubicin, Vinblastine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (Estramustine + Etoposide)
Arm Type
Experimental
Arm Description
Arm I: Oral Estramustine 3 x day + oral Etoposide 2 x day on days 1-14 + Paclitaxel IV over 1 hour Day 2, repeats every 21 days.
Arm Title
Arm II (Chemotherapy + Ketoconazole)
Arm Type
Experimental
Arm Description
Arm II: Doxorubicin IV Days 1, 15, and 29, Vinblastine IV Days 8, 22, and 36, Oral Ketoconazole 3 x day on Days 1-7, 15-21, + 29-35, and Oral Estramustine 3 x day on Days 8-14, 22-28, and 36-42; 6 weeks of alternating chemotherapy and 2 weeks rest, for 8 week course.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
Adriamycin, Rubex
Intervention Description
Doxorubicin IV on days 1, 15, and 29.
Intervention Type
Drug
Intervention Name(s)
Estramustine phosphate sodium
Other Intervention Name(s)
Emcyt
Intervention Description
Arm I: Oral estramustine three times a day for 21 day cycle. Arm II: Oral estramustine three times a day on days 8-14, 22-28, and 36-42 in 8 week cycle.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
VePeside
Intervention Description
Oral etoposide twice daily on days 1-14.
Intervention Type
Drug
Intervention Name(s)
Ketoconazole
Other Intervention Name(s)
Nizoral
Intervention Description
Oral ketoconazole three times a day on days 1-7, 15-21, and 29-35.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
IV over 1 hour on day 2.
Intervention Type
Drug
Intervention Name(s)
Vinblastine
Other Intervention Name(s)
Velban
Intervention Description
IV on days 8, 22, and 36.
Primary Outcome Measure Information:
Title
Prostate specific antigen (PSA)- based Response Rate
Time Frame
8 week cycle

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randall E. Millikan, MD, PhD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12610188
Citation
Millikan R, Thall PF, Lee SJ, Jones D, Cannon MW, Kuebler JP, Wade J 3rd, Logothetis CJ. Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer. J Clin Oncol. 2003 Mar 1;21(5):878-83. doi: 10.1200/JCO.2003.04.057.
Results Reference
result
Links:
URL
http://www.mdanderson.org
Description
UT MD Anderson Cancer Center Website

Learn more about this trial

Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

We'll reach out to this number within 24 hrs