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

Prostate Cancer Clinical Trial

Official title:

A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00052845
• Other study ID #: CALGB-90004
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2003
• Last updated: June 30, 2016
• Start date: November 2002
• Est. completion date: April 2009

Study information

• Verified date: June 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 2009
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel
70 mg/sq m IV infusion over 1 hour Day 2 of ea cycle
• estramustine phosphate sodium
280 mg PO tid Days 1-5 of ea cycle
• exisulind
Two 125 mg capsules PO bid Days 1-21 of ea cycle

Locations

Country	Name	City	State
Canada	McGill University	Montreal	Quebec
Puerto Rico	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates	Concord	North Carolina
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas	Dallas	Texas
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth Medical School	Lebanon	New Hampshire
United States	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	Ministry Medical Group - Northern Region	Rhinelander	Wisconsin
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Saint Anthony Medical Center	Rockford	Illinois
United States	Lakeland Medical Center - St. Joseph	Saint Joseph	Michigan
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Lombardi Cancer Center of Georgetown University Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (3)

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.

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 S

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression		24 months from study entry	No
Secondary	Toxicity		treatment up to 3 mon post treatment	Yes
Secondary	Changes in PSA		During treatment then q 3 mon until ds progression	No
Secondary	Overall Survival		24 months from study entry	No