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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00460031
First received: April 11, 2007
Last updated: May 16, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: ketoconazole
Drug: lenalidomide
Drug: therapeutic hydrocortisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients With Prostate Cancer Progressive After Androgen Deprivation

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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:
  • Time to Progression [ Time Frame: One year (12 months) after start of treatment ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: Up to 30 days after discontinuation of treatment ] [ Designated as safety issue: Yes ]
    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.

  • Change in Immune Response From Baseline [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the levels of CD4+ FoxP3+ Regulatory T cells

  • Ratio of Change in Immune Response From Baseline [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    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


Enrollment: 34
Study Start Date: September 2006
Estimated Study Completion Date: December 2016
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketoconazole Plus Lenalidomide Drug: ketoconazole
400 tid
Other Name: held for toxicity, missed days of therapy are not made up.
Drug: lenalidomide
Lenalidomide will be administered daily at a dose of 25mg po qd on days 1-21 of the cycle.
Drug: therapeutic hydrocortisone
20mg qam 10mg qhs

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

PATIENTS WITH PROSTATE CANCER PROGRESSIVE AFTER ANDROGEN DEPRIVATION Inclusion Criteria Understand and voluntarily sign an informed consent form. Age 18 years at the time of signing the informed consent form. Histologically confirmed adenocarcinoma of the prostate. Testosterone less than 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy. All previous cancer therapy, including radiation, and surgery, must have been discontinued at least 4 weeks prior to receive first dose of study drug.

Progressive disease after androgen deprivation.

Exclusion Criteria Prior systemic chemotherapy for hormone refractory prostate cancer. Prior neoadjuvant and adjuvant chemotherapy are allowed when completed at least 12 months prior to enrollment.

Prior ketoconazole, aminoglutethimide or corticosteroids for the treatment of progressive prostate cancer.

Prior immunotherapy including, but not limited to, vaccines, Thalidomide, and or Lenalidomide like agents.

Supplements or complementary medicines/botanicals are not permitted while on protocol therapy, except for any combination of the following:

conventional multivitamin supplements selenium lycopene soy supplements Patients should review the label with their doctor prior to enrollment, and discontinue disallowed agents prior to study enrollment Serious intercurrent infections or non-malignant medical illnesses including autoimmune disorders that are uncontrolled.

Psychiatric illnesses/social situations that would limit compliance with protocol requirements.

Evidence of CNS (brain or Leptomeningeal) metastases or large pleural/pericardial effusions.

Known contraindication to receive Ketoconazole or Lenalidomide Concurrent use of ketoconazole with statin compounds is absolutely contraindicated. Thus, patients receiving Statin drugs (fluvastatin, atorvastatin, and simvastatin) should discontinue them for at least 7 days before starting ketoconazole.

Patients taking astemizole, terfenadine, or cisapride, rifampin or isoniazid are not eligible, unless they agreed to completely discontinue those agents. In that case, any of these agents should be discontinued at least 7 days prior to start therapy with Ketoconazole.

Use of any other experimental drug or therapy within 28 days of baseline. Known hypersensitivity to thalidomide or its analogues. Any prior use of Lenalidomide. Known positive for HIV or infectious hepatitis, type A, B or C. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the breast.

  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: NCT00460031

Locations
United States, Ohio
Lake/University Ireland Cancer Center
Cleveland, Ohio, United States, 44060
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
University Suburban Health Center
Cleveland, Ohio, United States, 44121
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
UHHS Westlake Medical Center
Cleveland, Ohio, United States, 44145
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jorge Garcia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Matthew M. Cooney, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00460031     History of Changes
Other Study ID Numbers: CASE12805  P30CA043703 
Study First Received: April 11, 2007
Results First Received: July 14, 2014
Last Updated: May 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
adenocarcinoma of the prostate
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Hydrocortisone 17-butyrate 21-propionate
Genital Diseases, Male
Prostatic Diseases
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Lenalidomide
Thalidomide
Ketoconazole
Anti-Inflammatory Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016