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Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Registration Number
NCT00460031
Lead Sponsor
Case Comprehensive Cancer Center
Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as ketoconazole, may stop the adrenal glands from making androgens. Lenalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving ketoconazole and hydrocortisone together with lenalidomide may be an effective treatment for prostate cancer.

PURPOSE: This phase II trial is studying how well giving ketoconazole and hydrocortisone together with lenalidomide works in treating patients with prostate cancer that did not respond to hormone therapy.

Detailed Description

OBJECTIVES:

Primary

* Determine the objective response frequency in patients with hormone-refractory progressive prostate cancer treated with ketoconazole, hydrocortisone, and lenalidomide.

Secondary

* Determine the effect of this regimen on time to clinical progression in these patients.

* Determine the safety of this regimen in these patients.

* Determine the effects of this regimen on serum cytokines, including tumor necrosis factor-alpha, basic fibroblast growth factor, plasma soluble interleukin (IL)-2 receptor, IL-8, and IL-12, as well as serum vascular endothelial growth factor levels in these patients.

* Determine the co-stimulatory effects of this regimen on dendritic cells and CD4-positive, CD25-positive, T-regulatory cells in these patients.

OUTLINE: This is a nonrandomized, open-label study.

Patients receive oral ketoconazole 3 times daily and oral hydrocortisone twice daily on days 1-28 and oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for evaluation of prostate cancer-specific immune response. Blood samples are assessed by serum analysis, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay techniques to detect and quantify different cytokines, antiangiogenic markers, dendritic cells, and specific T-regulatory cells.

After completion of study therapy, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
34
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ketoconazole Plus Lenalidomideketoconazole-
Ketoconazole Plus Lenalidomidelenalidomide-
Ketoconazole Plus Lenalidomidetherapeutic hydrocortisone-
Primary Outcome Measures
NameTimeMethod
Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease28 days

Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.

Secondary Outcome Measures
NameTimeMethod
Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0Up to 30 days after discontinuation of treatment

Patients will be evaluated for toxicity every 2 weeks during the first cycle. Thereafter, evaluations will be done every 28 days or more frequently if clinically indicated.

Time to ProgressionOne year (12 months) after start of treatment

Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.

Ratio of Change in Immune Response From BaselineWeek 8

The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the ratio of BDCA-2 to BDCA-1 cells

Change in Immune Response From BaselineWeek 8

The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the levels of CD4+ FoxP3+ Regulatory T cells

Trial Locations

Locations (6)

UHHS Westlake Medical Center

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

🇺🇸

Cleveland, Ohio, United States

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

🇺🇸

Cleveland, Ohio, United States

Lake/University Seidman Cancer Center

🇺🇸

Cleveland, Ohio, United States

University Suburban Health Center

🇺🇸

Cleveland, Ohio, United States

UHHS Chagrin Highlands Medical Center

🇺🇸

Cleveland, Ohio, United States

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