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Prostate CancerPhase 3NCT00004635

Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer

A Phase 3 study testing Thalidomide, leuprolide acetate and goserelin in people with Prostate Cancer, run by National Cancer Institute (NCI) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Thalidomide, leuprolide acetate and goserelin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
159 participants
Where
9 sitesUnited States
Study dates
1 Mar 2000to 30 Mar 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 20Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • National Institutes of Health, Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • Wayne State University Hutzel Hospital

    Detroit, Michigan, 48201

  • Holy Cross Hospital, Fort Lauderdale

    Fort Lauderdale, Florida, 33308

  • University of Minnesota

    Minneapolis, Minnesota, 55415

  • Louisiana State University

    New Orleans, Louisiana, 70112-2282

  • Columbia University

    New York, New York, 10032-3784

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15261

  • Naval Medical Center, Portsmouth

    Portsmouth, Virginia, 23708

  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

About this study

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 computed tomography (CT) scans or other imaging studies.

Read more

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.

Read the 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.

Conditions
Prostate Cancer
Being tested
Thalidomide, leuprolide acetate, goserelin, Placebo
Keywords
Angiogenesis, Cancer, Hormonal Therapy, Prostate, Thalidomide, Prostate Cancer
Medical subject headings
Prostatic Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThalidomideDrug

    Also called Thalomid

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

  • leuprolide acetateDrug

    Also called leuprorelin

    Injections of leuprolide once a month for six months.

  • goserelinDrug

    Also called Zolodex

    Injections of Goserelin once a month for six months.

  • PlaceboOther

    Also called Sugar pill

    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.

Study groups in NCT00004635
Study groupRoleWhat they receive
ThalidomideExperimentalStudy 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.
Receives: Drug: Thalidomide; Drug: leuprolide acetate; Drug: goserelin
PlaceboExperimentalStudy 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.
Receives: Drug: leuprolide acetate; Drug: goserelin; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 36 months

Secondary outcomes (1)

  1. The Number of Participants With Adverse Events

    Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2000 (estimated)
  2. Study start1 Mar 2000
  3. Primary completion30 Jan 2005
  4. Study completion30 Mar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004635
Sponsor's protocol ID
000080
Other IDs
00-C-0080, 000080
Status last verified
Apr 2018
First submitted
19 Feb 2000
Last updated
22 May 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 6093713

  • 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.

    PubMed 5652850

  • 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.

    PubMed 9714301

  • 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.

    PubMed 19167733

  • 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.

    PubMed 31899823

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Thalidomide, leuprolide acetate and goserelin in people with Prostate Cancer, run by National Cancer Institute (NCI) at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Progression (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004635, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2018.

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