Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Thalidomide; leuprolide acetate; goserelin; Placebo
Intervention description: Thalidomide 200 mg given orally every evening at 9pm. Treatment may continue indefinitely provided that there are no dose-limiting toxicity.; Injections of leuprolide once a month for six months.; Injections of Goserelin once a month for six months.; Patients will receive the placebo if they initially received thalidomide. The starting dose of placebo 200 mg (four capsules of 100-50 mg capsules) orally once daily at bedtime.
Intervention MeSH terms: Thalidomide; Leuprolide; Goserelin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 159.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Angiogenesis; Cancer; Hormonal Therapy; Prostate; Thalidomide; Prostate Cancer

Summary:

      This multi-center study will evaluate whether thalidomide can improve the effectiveness of
      the drugs leuprolide or goserelin in treating testosterone-dependent prostate cancer.
      Leuprolide and goserelin-both approved to treat prostate cancer-reduce testosterone
      production, which, in most patients, reduces the size of the tumor. Thalidomide, a drug used
      for many years to treat leprosy, blocks the growth of blood vessels that may be important to
      disease progression.

      Patients 18 years or older with testosterone-dependent prostate cancer that has persisted or
      recurred after having had surgery, radiation therapy, or cryosurgery, but whose disease has
      not metastasized (spread beyond the prostate) may be eligible for this study. Candidates are
      screened with a medical history and physical examination, including blood tests, bone and
      computed tomography (CT) scans or other imaging studies.

      Study participants are randomly assigned to one of two treatment groups. One group receives
      leuprolide or goserelin followed by thalidomide; the other receives leuprolide or goserelin
      followed by placebo (a look-alike pill with no active ingredients). Patients in both groups
      receive an injection of leuprolide or goserelin once a month for 6 months. After that time
      they take four capsules of either thalidomide or placebo once a day and remain on the drug
      until their prostate-specific antigen (PSA) level returns to what it was before beginning
      leuprolide or goserelin or to 5 nanograms per liter, whichever is lower.(PSA is a protein
      secreted by the prostate gland. Monitoring changes in levels of this protein can help
      evaluate tumor progression). At this point the entire procedure begins again, starting with
      leuprolide or goserelin treatment, but the experimental drug is switched; patients originally
      treated with thalidomide are crossed over to placebo, and patients originally treated with
      placebo are crossed over to thalidomide.

      Patients are monitored periodically with the following tests and procedures:

      Medical histories and physical examinations. Blood and urine tests to monitor thalidomide and
      PSA levels, the response to treatment, and routine laboratory values (e.g., cell counts and
      kidney and liver function).

      Computed tomography (CT) and bone scans, and possibly other imaging tests to assess the
      tumor.

      Electromyography (EMG) and nerve conduction studies, as needed. For electromyography, a thin
      needle is inserted into a few muscles and the patient is asked to relax or to contract the
      muscles.
    

Eligibility criteria:

        -  Inclusion Criteria:

          -  patients must have prostate specific antigen (PSA) only androgen dependent
             adenocarcinoma of the prostate. All patients must have failed definitive therapy
             (radical prostatectomy, radiation therapy with external beam or brachytherapy,or
             cryosurgery).

          -  Patients must have a negative Computerized Tomography (CT) scan and Bone Scan for
             metastatic prostate cancer.

          -  Patients must have histopathological documentation of prostate cancer. Every attempt
             should be made to have slides and blocks reviewed at National Cancer Institute (NCI)
             Pathology laboratory. The review of pathology by the NCI will not delay enrollment.

          -  Patients must have progressive prostate cancer. Two consecutively rising PSAs above
             the nadir post-definitive therapy and an absolute value greater than 1.0 ng/ml
             separated by at least 2 weeks.

          -  Patients must have a life expectancy of more than 12 months.

          -  Patients must have a performance status of 0 to 2 according to the Eastern Cooperative
             Oncology Group (ECOG) criteria.

          -  Hematological eligibility parameters (within 2 weeks of starting therapy):

        Granulocyte count greater than or equal to 1,000/mm^3. Platelet count greater than or equal
        to 75,000/mm^3.

        - Biochemical eligibility parameters (within 2 weeks of starting therapy): If the
        creatinine is greater than 2.0 mg/dL obtain a 24 hour urine collection.

        Creatinine clearance must be greater than 40 mL/min. Hepatic function:

        bilirubin (total) less than or equal to 1 mg/dL upper limit of normal; Alanine
        aminotransferase (ALT) less than 2.5 times upper limit of normal.

          -  Exception: Patients with Clinical Gilbert's Syndrome may have total bilirubin less
             than or equal to 2.5 mg/dL.

          -  Patients must not have other concurrent malignancies (within the past 2 years) with
             the exception of nonmelanoma skin cancer and Rai Stage 0 chronic lymphoma leukemia),
             in situ carcinoma of any site, or life threatening illnesses, including untreated
             infection (must be at least 1 week off intravenous antibiotic therapy before beginning
             thalidomide).

          -  Patients with a history of unstable or newly diagnosed angina pectoris, recent
             myocardial infarction (within 6 months of enrollment), New York class II-IV congestive
             heart failure, chronic obstructive lung disease requiring oxygen therapy, uncontrolled
             seizure activity or by medical judgement of the physician, are not eligible.

          -  Patients must be able to understand and sign an informed consent document.

          -  Patients must be willing to travel from their home to the NIH or the participating
             institution (Louisiana State Univ., Univ. of Washington, Columbia University,Wayne
             State, University of Minnesota, University of Pittsburgh, Holy Cross)for follow-up
             visits (due to sedation associated with thalidomide). It is preferred that patients
             not drive the first 3 days of taking daily dosing,or if sedation appears to be a
             continuing complication).

          -  Patients must be greater than or equal to 18 years of age.

          -  Male patients must be counseled about the possibility that thalidomide may be present
             in semen. Men must use a latex condom every time they have sexual intercourse with
             women during therapy and for 8 weeks after discontinuing thalidomide, even if they
             have had a successful vasectomy.

          -  Patients may enroll as a late entry if the following criteria are met: Have received
             leuprolide or goserelin within 3 months of starting study,have a PSA within two weeks
             of hormonal injection and have a bone scan without metastasis within 8 weeks of
             enrollment.

          -  Patients with Rai Stage of Chronic Lymphocytic Leukemia (lymphocytosis only) will be
             eligible.

          -  Exclusion Criteria:

          -  Patients that have received leuprolide, diethylstilbestrol (DES), flutamide,
             bicalutamide, PC stands for prostate cancer and SPES is the Latin word for
             hope)PC-SPES, goserelin, cytotoxic chemotherapy, finasteride and/or nilutamide within
             the past year (or currently) are not eligible. Patients that received these agents for
             adjuvant or neoadjuvant therapy at the time of definitive therapy are eligible.
             Exception: Patients enrolled under late entry criteria, who have received
             leuprolide/goserelin within 3 months of starting study are eligible.

          -  Patients with National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP)
             grade 2 or greater peripheral neuropathy of any cause that is clinically detectable,
             patients receiving anti-convulsive medications, and patients with a history of
             seizures within the past 10 years will not be eligible for this study.

          -  Patients who are receiving sedative/hypnotic agents (i.e. benzodiazepines) which
             cannot be discontinued, will not be eligible for this study. Patients who have had a
             surgical orchiectomy will not be eligible for this study.

          -  Patients who received a systemic chemotherapy for prostate cancer will not be
             eligible.

          -  Patients with a confirmed psychiatric history of a major depression consistent with
             American Psychiatric Association Diagnostic and Statistical Manual (DSM IIIR
             criteria), confirmed by a psychiatrist will not be eligible.