Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00003084
First received: November 1, 1999
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Doxorubicin Hydrochloride
Drug: Estramustine phosphate sodium
Drug: Etoposide
Drug: Ketoconazole
Drug: Paclitaxel
Drug: Vinblastine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Taxol/VP-16/Estramustine vs. Ketoconazole/Doxorubicin/Vinblastine/Estramustine in Androgen Independent Prostate Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Prostate specific antigen (PSA)- based Response Rate [ Time Frame: 8 week cycle ] [ Designated as safety issue: No ]

Enrollment: 75
Study Start Date: December 1997
Study Completion Date: November 2002
Primary Completion Date: November 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Emcyt
Drug: Etoposide
Oral etoposide twice daily on days 1-14.
Other Name: VePeside
Drug: Paclitaxel
IV over 1 hour on day 2.
Other Name: 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: Doxorubicin Hydrochloride
Doxorubicin IV on days 1, 15, and 29.
Other Names:
  • Adriamycin
  • Rubex
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 Name: Emcyt
Drug: Ketoconazole
Oral ketoconazole three times a day on days 1-7, 15-21, and 29-35.
Other Name: Nizoral
Drug: Vinblastine
IV on days 8, 22, and 36.
Other Name: Velban

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003084

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Randall E. Millikan, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00003084     History of Changes
Other Study ID Numbers: DM97-022, P30CA016672, MDA-DM-97022, NCI-T97-0023, CDR0000065783
Study First Received: November 1, 1999
Last Updated: July 27, 2012
Health Authority: United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Doxorubicin
Estramustine
Etoposide
Etoposide phosphate
Ketoconazole
Liposomal doxorubicin
Paclitaxel
Vinblastine
14-alpha Demethylase Inhibitors
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014