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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Case Comprehensive Cancer Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00460031
First received: April 11, 2007
Last updated: May 2, 2012
Last verified: May 2012
  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: Allocation: Non-Randomized
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:
  • Objective response (complete and partial response) based on 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 willcontinue until criteria for progressive disease are met.


Secondary Outcome Measures:
  • Time to progression [ 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 willcontinue until criteria for progressive disease are met.

  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: during treatment and 30 days after treatment discontinues ] [ 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.


Enrollment: 34
Study Start Date: February 2007
Estimated Study Completion Date: July 2012
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Lake/University Ireland Cancer Center
Cleveland, Ohio, United States, 44060
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
UHHS Westlake Medical Center
Cleveland, Ohio, United States, 44145
University Suburban Health Center
Cleveland, Ohio, United States, 44121
Sponsors and Collaborators
Case Comprehensive Cancer Center
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

Additional Information:
No publications provided

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
Last Updated: May 2, 2012
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
Genital Diseases, Male
Prostatic Diseases
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Ketoconazole
Lenalidomide
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014