Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Ketoconazole, Hydrocortisone, and Lenalidomide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over NCI, Pharmaceutical / Industry CASE-12805 CASE 12805, CELGENE-CASE-12805, NCT00460031

Objectives

Primary

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

Secondary

1. Determine the effect of this regimen on time to clinical progression in these patients.
2. Determine the safety of this regimen in these patients.
3. 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.
4. Determine the co-stimulatory effects of this regimen on dendritic cells and CD4-positive, CD25-positive, T-regulatory cells in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate



• Progressive disease after androgen deprivation therapy, defined by 1 of the following:
  • Measurable progressive disease
  • No measurable disease AND meets 1 of the following criteria:
    • Elevated PSA with PSA level ≥ 2 ng/mL, rising on ≥ 2 consecutive occasions measured ≥ 2 weeks apart (if the third confirmatory PSA value is < the second value, then a fourth PSA value is required to document progression)
    • Positive bone scan with or without elevated PSA



• Demonstrates disease progression after antiandrogen withdrawal, as defined by 1 of the following:
  • Documented osseous or soft tissue progression
  • Two consecutive rising PSA values (obtained ≥ 2 weeks apart)



• Testosterone < 50 ng/dL
  • Must continue concurrent primary androgen deprivation with a luteinizing hormone releasing hormone analogue if no prior orchiectomy



• No large pleural or pericardial effusions



• No CNS (brain or leptomeningeal) metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• At least 4 weeks since prior cancer therapy, including radiotherapy and surgery
• At least 4 weeks since prior megestrol acetate, finasteride, any herbal product known to decrease PSA levels (e.g., saw palmetto or PC-SPES), or any systemic corticosteroids
• At least 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium) and recovered
• At least 6 weeks since prior bicalutamide or nilutamide
• At least 4 weeks since prior flutamide
• No prior systemic chemotherapy for prostate cancer
  • All other systemic chemotherapy must have been completed ≥ 5 years prior to study entry
• No prior ketoconazole, aminoglutethimide, or corticosteroids for treatment of progressive prostate cancer
• No prior immunotherapy including, but not limited to, vaccines, sargramostim (GM-CSF), thalidomide, and/or lenalidomide-like agents
• No prior lenalidomide
• At least 7 days since prior and no concurrent statin drugs (e.g., fluvastatin, atorvastatin, lovastatin, and simvastatin)
• At least 7 days since prior and no concurrent astemizole, terfenadine, cisapride, rifampin, or isoniazid
• More than 28 days since prior experimental drug or therapy
• No concurrent supplements or complementary medicines/botanicals, except for any combination of the following:
  • Conventional multivitamin supplements
  • Selenium
  • Lycopene
  • Soy supplements
• Concurrent bisphosphonates allowed provided the following criteria are met:
  • Patient is on a stable dose that shows tumor progression
  • No bisphosphonate therapy is initiated within 4 weeks of study entry
• Concurrent acetylsalicylic acid or warfarin allowed for deep vein thrombosis (DVT) prophylaxis provided the following criteria are met:
  • Daily acetylsalicylic acid is initiated on day 1 of study therapy
  • Patients with a history of DVT are on a stable-dose of warfarin
• No concurrent GM-CSF or other anticancer therapies, including radiotherapy, thalidomide, chemotherapy, immunotherapy, or other investigational agents
• No concurrent use of the following drugs:
  • Alprazolam
  • Diazepam
  • Temazepam
  • Triazolam
  • Midazolam
  • Ergot alkaloids
  • Pimozide

Patient Characteristics:

• Karnofsky performance status 70-100%
• Fertile patients must use effective contraception during and for 4 weeks after completion of study therapy (even if patient has undergone a prior successful vasectomy)
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• ALT and AST normal
• Creatinine ≤ 1.5 times upper limit of normal
• Bilirubin normal
• PT/INR and PTT normal (unless on anticoagulants)
• Calcium normal
• No other malignancies within the past 5 years except curatively treated basal cell or squamous cell skin cancer, stage Ta transitional cell carcinoma of the bladder, or carcinoma in situ of the breast
• No serious, concurrent infection or nonmalignant medical illness, including uncontrolled autoimmune disorders
• No known contraindication to ketoconazole or lenalidomide
• No known hypersensitivity to thalidomide or its analogues
• No known positivity for HIV or infectious hepatitis type A, B, or C
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

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

Outcomes

Objective response (complete and partial response) based on PSA or measurable disease

Time to progression
Toxicity as assessed by NCI CTCAE v3.0
Pattern of immune response, in terms of T-cell and dendritic-cell markers and serum levels of tumor necrosis factor-alpha, basic fibroblast growth factor, plasma soluble interleukin (IL)-2 receptor, IL-8, IL-12, and vascular endothelial growth factor
Change in mean T-cell immunohistochemical markers and dendritic cells over time

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.

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Matthew Cooney, MD, Principal investigator		Ph: 216-844-5412

U.S.A.
Ohio
	Canton
	Mercy Cancer Center at Mercy Medical Center
		Matthew Cooney	Ph:  216-691-0100
	Chardonr
	Geauga Regional Hospital
		Matthew Cooney	Ph:  216-691-0100
	Cleveland
	Case Comprehensive Cancer Center
		Clinical Trials Office - Case Comprehensive Cancer Center	Ph:  800-641-2422
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100
	Mentor
	Lake/University Ireland Cancer Center
		Matthew Cooney	Ph:  216-691-0100
	Middleburgh Heights
	Southwest General Health Center
		Matthew Cooney	Ph:  216-691-0100
	Orange Villager
	UHHS Chagrin Highlands Medical Center
		Matthew Cooney	Ph:  216-691-0100
	South Euclid
	University Suburban Health Center
		Matthew Cooney	Ph:  216-691-0100
	Westlaker
	UHHS Westlake Medical Center
		Matthew Cooney	Ph:  216-691-0100

Registry Information
Official Title		Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients with Prostate Cancer Progressive after Androgen Deprivation
Trial Start Date		2007-02-20
Registered in ClinicalTrials.gov		NCT00460031
Date Submitted to PDQ		2007-02-20
Information Last Verified		2008-05-24
NCI Grant/Contract Number		CA43703

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