Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00052845
First received: January 24, 2003
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Estramustine may fight prostate cancer by reducing the production of androgens. Exisulind may stop the growth of prostate cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining these therapies may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining estramustine with exisulind and docetaxel in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.


Condition Intervention Phase
Prostate Cancer
Drug: docetaxel
Drug: estramustine phosphate sodium
Drug: exisulind
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Time to progression [ Time Frame: 24 months from study entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: treatment up to 3 mon post treatment ] [ Designated as safety issue: Yes ]
  • Changes in PSA [ Time Frame: During treatment then q 3 mon until ds progression ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 24 months from study entry ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: November 2002
Study Completion Date: April 2009
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combined chemotherapy
combination of 3 chemotherapy agents for hormone refractory prostate cancer
Drug: docetaxel
70 mg/sq m IV infusion over 1 hour Day 2 of ea cycle
Drug: estramustine phosphate sodium
280 mg PO tid Days 1-5 of ea cycle
Drug: exisulind
Two 125 mg capsules PO bid Days 1-21 of ea cycle

Detailed Description:

OBJECTIVES:

  • Determine the time to objective and biochemical progression and response proportion (objective and post-therapy changes in PSA) in patients with hormone refractory metastatic prostate cancer treated with docetaxel, estramustine, and exisulind.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the overall survival of patients treated with this regimen.

OUTLINE: Patients receive oral estramustine 3 times daily on days 1-5, docetaxel IV over 1 hour on day 2, and oral exisulind twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study within 18 months.

  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

    • Progressive systemic (metastatic) disease despite castrate levels of testosterone secondary to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist therapy

      • Castrate levels of testosterone must be maintained
      • LHRH analog therapy should be continued
    • Failed prior standard androgen-deprivation therapy
    • Serum testosterone no greater than 50 ng/mL for patients who have not had bilateral orchiectomy
  • Evidence of metastatic disease on CT scan, MRI, or bone scan (no positron-emission tomography or prostascint)
  • Evidence of progressive disease after most recent prior therapy (including hormonal therapy) as defined by 1 of the following:

    • Measurable disease progression

      • More than 20% increase in the sum of the longest diameters of target lesions from the time of maximal regression or the appearance of 1 or more new lesions
    • Bone scan progression

      • Appearance of 1 or more new lesions on bone scan attributable to prostate cancer AND
      • PSA at least 5 ng/mL
    • PSA progression

      • PSA at least 5 ng/mL which has increased serially from baseline on 2 occasions (at least 1 week apart) NOTE: If the confirmatory PSA is less than screening PSA, an additional test for rising PSA is required

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • AST and ALT no greater than 1.5 times upper limit of normal (ULN)
  • Bilirubin no greater than ULN

Renal

  • Creatinine no greater than 1.5 times ULN

Cardiovascular

  • No myocardial infarction within the past year
  • No significant change in anginal pattern within the past year
  • No congestive heart failure
  • No New York Heart Association class II-IV heart disease
  • No deep vein thrombosis within the past year

Pulmonary

  • No pulmonary embolus within the past year

Other

  • No clinically significant peripheral neuropathy
  • No known hypersensitivity to sulindac
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior cytotoxic chemotherapy (including estramustine or suramin)
  • No other concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 4 weeks since prior flutamide and megestrol
  • At least 6 weeks since prior bicalutamide and nilutamide
  • At least 4 weeks since prior hormonal therapy known to decrease PSA levels (including ketoconazole, aminoglutethimide, finasteride, or any systemic corticosteroid)
  • Concurrent primary testicular androgen suppression therapy (e.g., with a LHRH analog) allowed
  • No other concurrent hormonal therapy except:

    • Steroids for adrenal insufficiency
    • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
    • Intermittent dexamethasone as an antiemetic

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered
  • At least 8 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
  • No concurrent palliative radiotherapy

Surgery

  • See Disease Characteristics
  • At least 4 weeks since prior major surgery and recovered

Other

  • At least 4 weeks since prior herbal product known to decrease PSA levels (including saw palmetto, PC-SPES)
  • More than 1 week since prior sulindac
  • No concurrent sulindac
  • No concurrent chronic nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors and salicylates such as aspirin, mesalamine, salsalate, and sulfasalazine)

    • Concurrent ibuprofen and naproxen allowed
    • Low-dose aspirin (e.g., 81 mg/day) for cardiovascular prevention allowed
  • No concurrent full-dose oral or parenteral anticoagulation therapy
  • Concurrent bisphosphonate therapy allowed provided therapy was initiated at least 4 weeks before study and disease has progressed despite therapy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00052845

  Hide Study Locations
Locations
United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
Veterans Affairs Medical Center - Washington, DC
Washington, District of Columbia, United States, 20422
Lombardi Cancer Center of Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307-5000
United States, Florida
Broward General Medical Center
Fort Lauderdale, Florida, United States, 33316
Memorial Regional Hospital Comprehensive Cancer Center
Hollywood, Florida, United States, 33021
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Illinois
MBCCOP - University of Illinois at Chicago
Chicago, Illinois, United States, 60612-7323
Louis A. Weiss Memorial Hospital
Chicago, Illinois, United States, 60640
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
West Suburban Center for Cancer Care
River Forest, Illinois, United States, 60305
Saint Anthony Medical Center
Rockford, Illinois, United States, 61108
United States, Indiana
Fort Wayne Medical Oncology and Hematology, Incorporated
Fort Wayne, Indiana, United States, 46885-5099
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Baptist Hospital East - Louisville
Louisville, Kentucky, United States, 40207
United States, Maryland
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
Veterans Affairs Medical Center - Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
University of Massachusetts Memorial Medical Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, Michigan
Lakeland Medical Center - St. Joseph
Saint Joseph, Michigan, United States, 49085
United States, Minnesota
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Veterans Affairs Medical Center - Columbia (Truman Memorial)
Columbia, Missouri, United States, 65201
Missouri Baptist Cancer Center
Saint Louis, Missouri, United States, 63131
Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
Veterans Affairs Medical Center - Las Vegas
Las Vegas, Nevada, United States, 89106
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth Medical School
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
United States, New York
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Elmhurst Hospital Center
Elmhurst, New York, United States, 11373
Queens Cancer Center of Queens Hospital
Jamaica, New York, United States, 11432
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
North Shore University Hospital
Manhasset, New York, United States, 11030
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai Medical Center, NY
New York, New York, United States, 10029
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
Syracuse, New York, United States, 13217
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Veterans Affairs Medical Center - Asheville
Asheville, North Carolina, United States, 28805
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, United States, 27599-7295
NorthEast Oncology Associates
Concord, North Carolina, United States, 28025
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Cape Fear Valley Health System
Fayetteville, North Carolina, United States, 28302-2000
Lenoir Memorial Hospital Cancer Center
Kinston, North Carolina, United States, 28503-1678
FirstHealth Moore Regional Hospital
Pinehurst, North Carolina, United States, 28374
New Hanover Regional Medical Center
Wilmington, North Carolina, United States, 28402-9025
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
United States, North Dakota
Veterans Affairs Medical Center - Fargo
Fargo, North Dakota, United States, 58102
United States, Ohio
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Lifespan: The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas
Dallas, Texas, United States, 75235-9154
Veterans Affairs Medical Center - Dallas
Dallas, Texas, United States, 75216
United States, Vermont
Green Mountain Oncology Group
Bennington, Vermont, United States, 05201
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05401-3498
Veterans Affairs Medical Center - White River Junction
White River Junction, Vermont, United States, 05009
United States, Virginia
Martha Jefferson Hospital
Charlottesville, Virginia, United States, 22902
Virginia Oncology Associates - Norfolk
Norfolk, Virginia, United States, 23502
MBCCOP - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Oncology and Hematology Associates of Southwest Virginia, Inc.
Roanoke, Virginia, United States, 24014
United States, West Virginia
St. Mary's Medical Center
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Ministry Medical Group - Northern Region
Rhinelander, Wisconsin, United States, 54501
Canada, Quebec
McGill University
Montreal, Quebec, Canada, H2W 1S6
Puerto Rico
University of Puerto Rico School of Medicine Medical Sciences Campus
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Nancy A. Dawson, MD University of Maryland Greenebaum Cancer Center
  More Information

Additional Information:
Publications:
Dawson NA, Halabi S, Biggs DD, et al.: A phase II study of estramustine (E), docetaxel (D) and exisulind in hormone-refractory prostate cancer (HRPC): toxicity results of CALGB 90004. [Abstract] American Society of Clinical Oncology 2005 Prostate Cancer Symposium, 17-19 February 2005, Orlando, Florida. A-289, 2005.
Dawson NA, Halabi S, Biggs DD, et al.: A phase II Study of estramustine (E), docetaxel (D) and exisulind in hormone-refractory prostate cancer (HRPC): initial results of CALGB 90004 . [Abstract] J Clin Oncol 23 (Suppl 16): A-4649, 415s, 2005.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00052845     History of Changes
Other Study ID Numbers: CDR0000258766, U10CA031946, CALGB-90004
Study First Received: January 24, 2003
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Docetaxel
Estramustine
Hormones
Sulindac sulfone
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticarcinogenic Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014