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

RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Leuprolide and goserelin may fight prostate cancer by reducing the production of androgens. Thalidomide may stop the growth of prostate cancer by stopping blood flow to the tumor. It is not yet known whether leuprolide or goserelin plus thalidomide is more effective than leuprolide or goserelin alone for prostate cancer.

PURPOSE: This randomized phase III trial is studying leuprolide or goserelin plus thalidomide to see how well they work compared to leuprolide or goserelin alone in treating patients with nonmetastatic prostate cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

OBJECTIVES: - Determine the potential clinical activity of oral thalidomide, in terms of time to progression, in patients with androgen-dependent nonmetastatic prostate cancer. - Evaluate the toxic effects of oral thalidomide in these patients after definitive therapy. - Determine whether changes in molecular markers of angiogenesis are observed in patients treated with this regimen. - Assess pharmacodynamic correlations between activity and toxicity of this regimen in these patients.

OUTLINE: This is a randomized, crossover, double-blind, placebo-controlled, multicenter study.

Patients with a rising prostate-specific antigen (PSA) are randomized to receive leuprolide or goserelin intramuscularly monthly for 6 months, followed by oral thalidomide or oral placebo daily. At the time of PSA progression, patients receive an additional 6 months of monthly leuprolide or goserelin therapy. After 6 months, patients originally treated with thalidomide are crossed over to the placebo arm or vice versa until PSA progression or development of metastatic disease is observed.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly until disease progression.

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study within 18 months.

Intervention(s) in this Clinical Trial

• Drug: goserelin
• Drug: leuprolide acetate
• Drug: thalidomide

DISEASE CHARACTERISTICS:

• Histologically confirmed nonmetastatic (stage D0 by Jewett classification system;
• stage IV by TNM classification system) adenocarcinoma of the prostate
• Must be prostate-specific antigen (PSA) only androgen dependent
• Failed definitive therapy (radical prostatectomy, radiotherapy with external beam or brachytherapy, or cryosurgery)
• No metastatic prostate cancer on CT scan or bone scan
• Progressive disease defined as:
• Two consecutively rising PSAs above the nadir post definitive therapy and greater than 1.0 ng/mL (at least 2 weeks apart)
• Eligible for late entry provided the following are true:
• Must have received leuprolide or goserelin within the past 3 months
• No metastasis by bone scan and CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 12 months

Hematopoietic:

• Granulocyte count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 1 mg/dL (2.5 mg/dL for patients with Gilbert's syndrome)
• ALT and AST less than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance greater than 40 mL/min

Cardiovascular:

• No unstable angina pectoris
• No myocardial infarction within the past 6 months
• No New York Heart Association class II-IV congestive heart failure

Pulmonary:

• No chronic obstructive lung disease requiring oxygen therapy

Neurologic:

• No peripheral neuropathy grade 2 or greater
• No uncontrolled seizure disorders within the past 10 years

Other:

• Patients must use a latex condom during and for 4 weeks after study participation
• Fertile patients must use effective barrier contraception for 4 weeks before, during, and for 2 months after study participation
• No other malignancy within the past 2 years except nonmelanoma skin cancer, carcinoma in situ, or Rai stage 0 chronic lymphocytic leukemia
• No other life threatening illness
• No uncontrolled infection
• No psychiatric history of major depression, confirmed by psychiatrist

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy for prostate cancer
• At least 1 year since other prior cytotoxic chemotherapy
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 1 year since prior leuprolide*, diethylstilbestrol, flutamide, bicalutamide, goserelin*, finasteride, or nilutamide unless received as adjuvant or neoadjuvant therapy
• No other concurrent leuprolide, diethylstilbestrol, flutamide, bicalutamide, goserelin, finasteride, or nilutamide NOTE: *Does not include patients enrolled under late entry criteria who have received leuprolide/goserelin within the past 3 months

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics
• No prior bilateral surgical orchiectomy

Other:

• At least 1 year since prior PC-SPES or sedative/hypnotics, unless received as adjuvant or neoadjuvant therapy
• At least 1 week since prior IV antibiotics
• No concurrent PC-SPES
• No concurrent sedative or hypnotic agents (i.e., benzodiazepines)
• No concurrent anticonvulsants

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 Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

William Dahut, MD Study Chair National Cancer Institute (NCI)  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00020085

Study ID Number: CDR0000067700

ClinicalTrials.gov Identifier: NCT00020085

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database