Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer

NCT00004635 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 00008000-C-0080
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Prostate Cancer

Keywords

Angiogenesis; Cancer; Hormonal Therapy; Prostate; Thalidomide; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  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.

  36 months

Secondary Outcomes (1)

• The Number of Participants With Adverse Events

  Date treatment consent signed to date off study, approximately 60 months

Study Arms (2)

Thalidomide

EXPERIMENTAL

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; Drug: leuprolide acetate; Drug: goserelin

Placebo

EXPERIMENTAL

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; Drug: goserelin; Other: Placebo

Interventions

Thalidomide DRUG

Thalidomide 200 mg given orally every evening at 9pm. Treatment may continue indefinitely provided that there are no dose-limiting toxicity.

Also known as: Thalomid

Thalidomide

leuprolide acetate DRUG

Injections of leuprolide once a month for six months.

Also known as: leuprorelin

Placebo; Thalidomide

goserelin DRUG

Injections of Goserelin once a month for six months.

Also known as: Zolodex

Placebo; Thalidomide

Placebo OTHER

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.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Holy Cross Hospital, Fort Lauderdale: collaborator
• Louisiana State University Health Sciences Center in New Orleans: collaborator
• Wayne State University: collaborator
• University of Minnesota: collaborator
• Columbia University: collaborator
• University of Pittsburgh: collaborator
• United States Naval Medical Center, Portsmouth: collaborator
• University of Washington: collaborator

Study Sites (9)

Holy Cross Hospital, Fort Lauderdale

Fort Lauderdale, Florida, 33308, United States

Location

Louisiana State University

New Orleans, Louisiana, 70112-2282, United States

Location

National Institutes of Health, Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Wayne State University Hutzel Hospital

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55415, United States

Location

Columbia University

New York, New York, 10032-3784, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Naval Medical Center, Portsmouth

Portsmouth, Virginia, 23708, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (5)

• Aronson IK, Yu R, West DP, Van den Broek H, Antel J. Thalidomide-induced peripheral neuropathy. Effect of serum factor on nerve cultures. Arch Dermatol. 1984 Nov;120(11):1466-70. doi: 10.1001/archderm.120.11.1466.

  PMID: 6093713 BACKGROUND

• Bakay B, Nyhan WL. Binding of thalidomide by macromolecules in the fetal and maternal rat. J Pharmacol Exp Ther. 1968 Jun;161(2):348-60. No abstract available.

  PMID: 5652850 BACKGROUND

• Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol. 1998 Jun 1;55(11):1827-34. doi: 10.1016/s0006-2952(98)00046-x.

  PMID: 9714301 BACKGROUND

• Figg WD, Hussain MH, Gulley JL, Arlen PM, Aragon-Ching JB, Petrylak DP, Higano CS, Steinberg SM, Chatta GS, Parnes H, Wright JJ, Sartor O, Dahut WL. A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation. J Urol. 2009 Mar;181(3):1104-13; discussion 1113. doi: 10.1016/j.juro.2008.11.026. Epub 2009 Jan 23.

  PMID: 19167733 RESULT

• Hawley JE, Pan S, Figg WD, Lopez-Bujanda ZA, Strope JD, Aggen DH, Dallos MC, Lim EA, Stein MN, Hu J, Drake CG. Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy. Prostate. 2020 Mar;80(4):336-344. doi: 10.1002/pros.23948. Epub 2020 Jan 3.

  PMID: 31899823 DERIVED

Related Links

• MedlinePlus
• Drug Information Portal
• U.S. FDA Resources

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

Thalidomide; Leuprolide; Goserelin; Sugars

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Carbohydrates

Limitations and Caveats

A total of 159 participants were accrued beginning in March 2000 until January 2005. Accrual rates were less than anticipated and the study was closed to further entry by the Independent Data Safety and Monitoring Board for the NCI CCR.

Results Point of Contact

• Title: William L. Dahut, M.D.
• Organization: National Cancer Institute, National Institutes of Health

dahutw@mail.nih.gov

301-435-8183

Study Officials

• William L Dahut, M.D.

  National Cancer Institute, National Institutes of Heath

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 19, 2000
• First Posted: February 21, 2000
• Study Start: March 1, 2000
• Primary Completion: January 30, 2005
• Study Completion: March 30, 2010
• Last Updated: May 22, 2018
• Results First Posted: September 12, 2012

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)