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

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Prostate Cancer

Treatments

Drug: exisulind

Drug: docetaxel

Drug: estramustine phosphate sodium

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00052845

CDR0000258766 (Registry Identifier)

CALGB-90004

U10CA031946 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

80 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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