This study will examine the effectiveness of combination therapy with docetaxel, estramustine, and thalidomide in treating prostate cancer. Estramustine and docetaxel are anti-cancer drugs. Estramustine is used primarily to treat prostate cancer and docetaxel is used for various cancers, including prostate. Thalidomide, approved to treat leprosy, inhibits the formation of new blood vessels that feed tumors. It has been found to lessen pain and lower PSA (a protein that is elevated in prostate cancer) levels in some patients with prostate cancer.

Men with advanced prostate cancer that does not respond to hormonal therapy may be eligible for this study. Candidates are screened with computed tomography (CT or CAT) scans to determine the extent of cancer and with blood and urine tests to determine if the experimental treatment can be safely given.

Participants receive drug therapy in 4-week treatment cycles as follows:

- Docetaxel infusions intravenously (through a vein) over a 30-minute period on the second day of the week for 3 consecutive weeks out of every cycle (day 2 of weeks 1, 2, and 3 of each cycle)

- Estramustine by mouth in capsule form three times a day for the first 3 days of 3 consecutive weeks in the cycle (days 1, 2, and 3 of weeks 1, 2, and 3 of each cycle)

- Thalidomide by mouth in tablet form once a day every day of the study.

Additionally, patients take dexamethasone by mouth before and after the docetaxel infusion to prevent fluid retention caused by the drug and the blood thinner enoxaparin once a day. This is injected under the skin to prevent formation of blood clot that may be caused by estramustine and thalidomide. Patients come to the NIH Clinical Center for each docetaxel infusion or they may choose to receive the first weekly dose at the Clinical Center and the second and third infusions at their oncologist's office.

In addition to drug therapy, patients have the following tests and procedures:

- Periodic blood and urine tests to monitor the response to treatment and drug side effects

- Possibly magnetic resonance imaging (MRI) to determine the usefulness of this test in evaluating disease progress and response to treatment

- Possibly tumor biopsy (surgical removal of a small piece of tumor tissue) in patients with a tumor mass that is accessible and safe to biopsy.

Response to therapy is evaluated approximately every 3 months using various tests, such as bone and CT scans. If there are no severe side effects and the cancer has not progressed, treatment may continue for more than 6 months. After six treatment cycles, patients have monthly chest x-rays to monitor possible fluid collecting around the lining of the lungs, which may occur in some patients who take docetaxel more 6 months or more.

Condition	Treatment or Intervention	Phase
Prostatic Neoplasms	Drug: Docetaxel  Drug: Estramustine  Drug: Thalidomide	Phase II

Further Study Details: 

Expected Total Enrollment:  60

This is a Phase II study of estramustine, docetaxel and thalidomide in patients with androgen independent metastatic prostate cancer who are previously untreated with chemotherapy. The primary objective of the study is to show a statistically significant improvement in PSA decline when compared to the combination of docetaxel and thalidomide. We will also be looking at multiple secondary endpoints. These will include possible pharmacokinetic interactions among the study agents, potential correlation between patient genotype and efficacy of treatment. We will also be looking for circulating tumor cells in blood before and after treatment. Additionally we will be monitoring the tolerability of the regimen and survival duration as endpoints as well. We hope to use this trial to build on the promising results seen in our thalidomide/docetaxel protocol where there was a significant PSA decline and a trend toward survival benefit. This protocol also hopes to extend upon the large phase III Intergroup study underway looking at docetaxel/estramustine vs. mitoxantrone/prednisone.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Androgen independent metastatic adenocarcinoma of the prostate defined as progressive metastatic disease (see below for definition of progressive metastatic disease) while on GnRH agonists or post surgical castration.
Histopathological documentation of prostate cancer confirmed in the NCI Laboratory of Pathology at the National Institutes of Health or the Pathology Department at National Naval Medical Center, prior to starting this study. In addition, patients whose slides are lost or unavailable will be eligible for the study if they provide documentation of prostate cancer and if they meet criteria of clinically progressive prostate cancer as outlined in the section below.
Clinically progressive prostate cancer documented prior to entry. Progression must be documented by at least one of the following parameters:
- Two consecutively rising PSA levels. The first rising PSA must be a minimum of one week from a reference value. It is recognized that PSA fluctuations are such that the confirmatory PSA value might be less then the previous one. In these cases the patient would still be eligible provided the next PSA was greater than the first rising PSA value. Patients must have a PSA greater than 5.0.
- At least one new lesion on bone scan.
- Progressive measurable disease.
Must have undergone bilateral surgical castration or must continue on a GnRH agonist
Those patients receiving an anti-androgen agent and are entering the trial due to a rise in PSA must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks after stopping bicalutamide or nilutamide.
ECOG performance status of 0-2.
Recovered from any toxicity from surgery or radiotherapy.
May not have received any chemotherapy for metastatic prostate cancer.
Absolute neutrophil count greater than 1,500/mm(3)
Platelet count greater than 100,000/mm(3). No platelet transfusions will be permitted within the two weeks prior to enrollment on protocol.
Hemoglobin 7.5 g/dl. No transfusions will be allowed within the two weeks prior to enrollment on protocol
If the creatinine is greater than 1.5 mg/dL, a 24 hour urine collection must be obtained, and measured creatinine clearance must be at least 40 mL/min.
Hepatic function: Hepatic: Total bilirubin less than Upper level of normal for that particular institution. Patients with Gilbert's syndrome will be eligible with bilirubin less than or equal to3.0.
AST and ALT less than 2.5 times upper limit of normal.
If the Alkaline phosphatase is greater than 2.5 times the upper limit of normal, it must be fractionated and the hepatic alkaline phosphatase should be less than 2.5 times the upper limit of normal.
Must be willing to travel from their home to the NIH for follow-up visits.
At least 18 years of age.
Able and willing to follow instructions and conform to protocol.
Patients may have had no other active malignancy within the past 2 years with the exception of non-melanoma skin cancer and superficial bladder carcinoma.
No history of myocardial infarction within the past 6 months, uncontrolled CHF, thromboembolic disease or uncontrolled angina pectoris.
EXCLUSION CRITERIA:
Brain metastases.
Previously received docetaxel, estramustine or thalidomide.
Greater than/Equal to Grade 2 peripheral neuropathy
History of transient ischemic attacks (TIA) or cerebrovascular accident (CVA) within the past 2 years are ineligible
Patients with HIV on antiretroviral medications will be excluded due to potential interactions with docetaxel
Patients with a level of cognitive impairment that prevents them from understanding and following the instructions of the protocol, or that impairs them from signing an informed consent .

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  040132; 04-C-0132
Record last reviewed:  February 2, 2005
Last Updated:  February 4, 2005
Record first received:  March 3, 2004
ClinicalTrials.gov Identifier:  NCT00078650
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08