Clinical trial NCT00052845: Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy
Official title: A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Time to progression
timeFrame: 24 months from study entry
Secondary outcomes:
measure: Toxicity
timeFrame: treatment up to 3 mon post treatment
measure: Changes in PSA
timeFrame: During treatment then q 3 mon until ds progression
measure: Overall Survival
timeFrame: 24 months from study entry
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center of Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Veterans Affairs Medical Center - Baltimore
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth Medical School
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: Veterans Affairs Medical Center - Fargo
state: North Dakota
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas
state: Texas
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Rhinelander
country: United States
facility: Ministry Medical Group - Northern Region
state: Wisconsin
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
Study officials:
affiliation: University of Maryland Greenbaum Cancer Center
name: Nancy Dawson, MD
role: STUDY_CHAIR
References:
citation: Dawson NA, Halabi S, Ou SS, Biggs DD, Kessinger A, Vogelzang N, Clamon GH, Nanus DM, Kelly WK, Small EJ; Cancer And Leukemia Group B. A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004. Clin Genitourin Cancer. 2008 Sep;6(2):110-6. doi: 10.3816/CGC.2008.n.017.
citation: 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.
citation: 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.