Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
Holy Cross Hospital, Fort Lauderdale
Louisiana State University Health Sciences Center in New Orleans
Wayne State University
University of Minnesota - Clinical and Translational Science Institute
Columbia University
University of Pittsburgh
United States Naval Medical Center, Portsmouth
University of Washington
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00004635
First received: February 19, 2000
Last updated: August 13, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Thalidomide
Drug: leuprolide acetate
Drug: goserelin
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Time to Progression [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Time to progression is defined as follows: if the PSA returns to baseline (defined as the PSA value prior to starting leuprolide or goserelin) or increases to the absolute value of 5 ng/ml.


Secondary Outcome Measures:
  • The Number of Participants With Adverse Events [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
    Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.


Enrollment: 159
Study Start Date: February 2000
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thalidomide
Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received thalidomide orally 200 mg a day. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received the placebo for thalidomide once a day.
Drug: Thalidomide
Thalidomide 200 mg given orally every evening at 9pm. Treatment may continue indefinitely provided that there are no dose-limiting toxicity.
Other Name: Thalomid
Drug: leuprolide acetate
Injections of leuprolide once a month for six months.
Other Names:
  • leuprolide acetate
  • leuprorelin
Drug: goserelin
Injections of Goserelin once a month for six months.
Other Name: Zolodex
Experimental: Placebo
Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received placebo for thalidomide. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received thalidomide 200 mg once a day.
Drug: leuprolide acetate
Injections of leuprolide once a month for six months.
Other Names:
  • leuprolide acetate
  • leuprorelin
Drug: goserelin
Injections of Goserelin once a month for six months.
Other Name: Zolodex
Other: Placebo
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.
Other Name: Sugar pill

Detailed Description:

This is a double-blind randomized phase III study designed to determine if thalidomide can improve the efficacy of the luteinizing hormone releasing hormone (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: basic fibroblast growth factor (bFGF), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), and transforming growth factor beta (TGFbeta). Likewise we will monitor changes in testosterone and dihydrotestosterone (DHT) throughout the study. Neurological complications are the primary dose-limiting toxicity anticipated with chronic thalidomide administration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004635

Locations
United States, Florida
Holy Cross Hospital, Fort Lauderdale
Fort Lauderdale, Florida, United States, 33308
United States, Louisiana
Louisiana State University
New Orleans, Louisiana, United States, 70112-2282
United States, Maryland
National Institutes of Health, Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Michigan
Wayne State University Hutzel Hospital
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55415
United States, New York
Columbia University
New York, New York, United States, 10032-3784
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, Virginia
Naval Medical Center, Portsmouth
Portsmouth, Virginia, United States, 23708
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Holy Cross Hospital, Fort Lauderdale
Louisiana State University Health Sciences Center in New Orleans
Wayne State University
University of Minnesota - Clinical and Translational Science Institute
Columbia University
University of Pittsburgh
United States Naval Medical Center, Portsmouth
University of Washington
Investigators
Principal Investigator: William L Dahut, M.D. National Cancer Institute, National Institutes of Heath
  More Information

Additional Information:
Publications:
Responsible Party: William L. Dahut, M.D., National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00004635     History of Changes
Obsolete Identifiers: NCT00020085
Other Study ID Numbers: 000080, 00-C-0080, 000080
Study First Received: February 19, 2000
Results First Received: March 30, 2012
Last Updated: August 13, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Angiogenesis
Cancer
Hormonal Therapy
Prostate
Thalidomide
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Goserelin
Leuprolide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014