Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer

Official Title: “A Double Blinded Randomized Crossover Phase III Study of Oral Thalidomide Versus Placebo in Patients With Stage D0 Androgen Dependent Prostate Cancer Following Limited Hormonal Ablation”

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 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) - 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. ...

This is a double-blind randomized phase III study designed to determine if thalidomide can improve the efficacy of the LHRH agonist (leuprolide or goserelin) in hormone-responsive patients with a rising PSA after primary definitive therapy for prostate cancer. Patients with only a rising PSA will be randomized to LHRH agonist for six months followed by oral thalidomide 200 mg per day or placebo (Phase A). At the time of PSA progression, an LHRH agonist will be restarted for six additional months. After six months, patients originally treated with thalidomide will be crossed over to placebo and patients originally treated with placebo will be crossed over to thalidomide and followed until PSA progression or the development of metastatic disease, whichever occurs first (Phase B). Additional information will be obtained on changes in the circulating levels of the following growth factors:

bFGF, TNF, VEGF, and TGFbeta. Likewise we will monitor changes in testosterone and DHT throughout the study. Neurological complications are the primary dose-limiting toxicity anticipated with chronic thalidomide administration.

Intervention(s) in this Clinical Trial

• Drug: Thalidomide
  • N/A
• Drug: leuprolide acetate
  • N/A
• Drug: goserelin
  • N/A

INCLUSION CRITERIA

• Patients must have 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 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 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 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 1mg/dL upper limit of normal; 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 judgment 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 (LSU, Univ. of Washington, Columbia University, Wayne State, University of Minnesota, University of Pittsburg, Holy Cross) for follow-up visits (due to sedation associated with thalidomideit is preferred that patients not drive during the first 3 days of taking daily dosing, or if sedation appears to be a continuing complication).
• Patients must be greater than or equal to18 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 luprolide or goserelin within 3 months of starting study, have a PSA within two weeks of hormonal injection and have a bone scan and CT scan without metastasis within 8 weeks of enrollment.
• Patients with Rai Stage 0 Chronic Lymphocytic Leukemia (lymphocytosis only) will be eligible.

EXCLUSION CRITERIA

• Patients that have received leuprolide, DES, flutamide, bicalutamide, 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 luprolide/goserelin within 3 months of starting study are eligible.
• Patients with NCI/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 systemic chemotherapy therapy 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.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Cancer Institute (NCI) NIH

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00004635

Study ID Number: 000080

ClinicalTrials.gov Identifier: NCT00004635

Health Authority: United States: Federal Government

NIH Clinical Center Detailed Web Page