Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

July 27, 2012 updated by: M.D. Anderson Cancer Center

A Randomized Phase II Trial of Taxol/VP-16/Estramustine vs. Ketoconazole/Doxorubicin/Vinblastine/Estramustine in Androgen Independent Prostate Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas - MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I (Estramustine + Etoposide)
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.
Drug: Estramustine phosphate sodium

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.

Other Names:
  • Emcyt
Drug: Etoposide
Oral etoposide twice daily on days 1-14.
Other Names:
  • VePeside
Drug: Paclitaxel
IV over 1 hour on day 2.
Other Names:
  • Taxol
EXPERIMENTAL: Arm II (Chemotherapy + Ketoconazole)
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.
Drug: Estramustine phosphate sodium

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.

Other Names:
  • Emcyt
Drug: Doxorubicin Hydrochloride
Doxorubicin IV on days 1, 15, and 29.
Other Names:
  • Adriamycin
  • Rubex
Drug: Ketoconazole
Oral ketoconazole three times a day on days 1-7, 15-21, and 29-35.
Other Names:
  • Nizoral
Drug: Vinblastine
IV on days 8, 22, and 36.
Other Names:
  • Velban

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Prostate specific antigen (PSA)- based Response Rate
Time Frame: 8 week cycle
8 week cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1997

Primary Completion (ACTUAL)

November 1, 2002

Study Completion (ACTUAL)

November 1, 2002

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 21, 2004

First Posted (ESTIMATE)

May 24, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

July 30, 2012

Last Update Submitted That Met QC Criteria

July 27, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DM97-022
  • P30CA016672 (U.S. NIH Grant/Contract)
  • MDA-DM-97022 (OTHER: UT MD Anderson Cancer Center)
  • NCI-T97-0023
  • CDR0000065783 (REGISTRY: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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