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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology Identifier:
First received: January 24, 2003
Last updated: September 27, 2013
Last verified: September 2013

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:


  • 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.


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


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


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


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


  • Creatinine no greater than 1.5 times ULN


  • 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


  • No pulmonary embolus within the past year


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


Biologic therapy

  • Not specified


  • 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


  • 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


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


  • 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
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Please refer to this study by its identifier: NCT00052845

  Show 80 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Nancy A. Dawson, MD University of Maryland Greenebaum Cancer Center
  More Information

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 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 by Site
Prostatic Diseases
Urogenital Neoplasms
Sulindac sulfone
Alkylating Agents
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
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Physiological Effects of Drugs
Protective Agents
Sensory System Agents
Tubulin Modulators processed this record on May 25, 2016