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Ketoconazole With or Without Alendronate Sodium in Treating Patients With Metastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00019695
Recruitment Status : Terminated
First Posted : March 5, 2007
Last Update Posted : April 22, 2014
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Ketoconazole may suppress the production of hormones and may interfere in the growth of prostate cancer cells. Alendronate sodium may be effective in preventing bone metastases and bone pain associated with prostate cancer. It is not known if ketoconazole is more effective with or without alendronate sodium.

PURPOSE: Randomized phase II trial to study the effectiveness of ketoconazole with or without alendronate sodium in treating patients who have metastatic prostate cancer.

Condition or disease Intervention/treatment Phase
Stage IV Prostate Cancer Bone Metastases Adenocarcinoma of the Prostate Recurrent Prostate Cancer Drug: alendronate sodium Drug: ketoconazole Phase 2

Detailed Description:

OBJECTIVES: I. Determine whether there is any evidence that ketoconazole plus alendronate sodium produces acceptable disease responses as compared with ketoconazole alone in patients with androgen-independent metastatic adenocarcinoma of the prostate.

II. Characterize the pharmacokinetics/pharmacodynamics and assess the bone marrow concentrations of both agents.

III. Assess matrix metalloproteinase (MMP) inhibition potential of alendronate sodium by monitoring markers of angiogenesis, MMP breakdown, and changes in hydroxyproline.

PROTOCOL OUTLINE: This is a randomized, open-label study. Patients are randomized to one of two treatment arms.

Arm I: Patients receive a single oral dose of ketoconazole on day 1. Patients begin taking ketoconazole 3 times per day on day 8.

Arm II: Patients receive a single oral dose of alendronate sodium on day 1 and a single oral dose of ketoconazole on day 3. Patients begin taking alendronate sodium once every morning and ketoconazole 3 times per day on day 8.

Treatment continues on both arms in the absence of unacceptable toxicity or disease progression. Patients who experience a clinical complete remission (CR) receive treatment for an additional 60 days beyond documentation of a clinical CR.

Patients are followed every 2 months.


A total of 72 patients (36 per arm) will be accrued for this study within 3 years.

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Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of High-Dose Ketoconazole With or Without Alendronate Sodium in Patients With Androgen-Independent Metastastic Adenocarinoma of the Prostate
Study Start Date : March 1999
Actual Study Completion Date : March 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)


--Disease Characteristics-- Histologically confirmed adenocarcinoma of the prostate Androgen independent with at least 1 bone lesion that is felt to be associated with metastatic disease Refractory disease must be demonstrated after the withdrawal of flutamide, nilutamide, bicalutamide, or any other antiandrogen Clinically progressive disease for at least 1 month documented by rising PSA levels, at least 1 new metastatic deposit on Tc-99 bone scintigraphy, increasing measurable disease, or new areas of malignant disease Patients with PSA-negative disease (i.e., PSA less than 10 ng/mL) must have positive CT scans of soft tissue disease that can be used for disease staging, bone scan, or some other form of documentable disease progression (i.e., rising carcinoembryonic antigen, prostatic acid phosphatase) Testosterone in the range expected for castrated males No brain metastases or primary CNS malignancies No unresolved acute local complications that require urgent local medical therapy (such as severe bone pain, spinal cord compression, or urinary flow obstruction) --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: No prior ketoconazole for prostate cancer Endocrine therapy: See Disease Characteristics Treatment with LHRH agonist must continue for those patients who have not undergone surgical castration If LHRH agonist has been discontinued, it must be reinstituted with documented disease progression At least 4 weeks since prior hormonal therapy other than LHRH agonist and recovered Radiotherapy: Prior radiotherapy to the prostate allowed At least 4 weeks since prior radiotherapy and recovered Surgery: Prior radical prostatectomy allowed At least 4 weeks since prior surgery and recovered Other: At least 4 weeks since other prior anti-cancer therapy and recovered No prior transfusion with strontium chloride Sr 89 and/or samarium Sm 153 lexidronam pentasodium No concurrent phenytoin, theophylline, cisapride, triazolam, astemizole, loratadine, rifampin, isoniazid, erythromycin, terfenadine, midazolam, alprazolam, atorvastatin calcium, cerivastatin sodium, dofetilide, lovastatin, pimozide, simvastatin, or sirolimus No concurrent drugs that decrease gastric acid output or increase gastric pH (e.g., antacids, cimetidine, ranitidine, or antimuscarinics) No concurrent warfarin --Patient Characteristics-- Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic: Granulocyte count at least 1,000/mm3 Hemoglobin at least 8.0 g/dL (pretreatment transfusion allowed, provided hemoglobin is maintained for more than 30 days without additional transfusions and/or an active source of bleeding is identified and treated) Platelet count at least 75,000/mm3 Hepatic: Acute care panel (i.e., electrolytes, BUN) and urinalysis normal Bilirubin no greater than 1.2 mg/dL ALT less than 2.5 times upper limit of normal AST less than 2.5 times normal Renal: Creatinine no greater than 1.5 mg/dL and no proteinuria present OR Creatinine clearance greater than 40 mL/min and proteinuria less than 500 mg/day (proteinuria not an exclusion for patients with stents in place) Cardiovascular: No history of unstable or newly diagnosed 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 uncontrolled seizure activity No history of seizures within the past 10 years Other: No other prior malignancies within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder No other life-threatening illnesses No untreated infection HIV negative Willingness to travel from home to NIH for follow-up visits

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00019695

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United States, Maryland
Medicine Branch
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Study Chair: William D. Figg National Cancer Institute (NCI)
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00019695    
Obsolete Identifiers: NCT00001802
Other Study ID Numbers: CDR0000066964
First Posted: March 5, 2007    Key Record Dates
Last Update Posted: April 22, 2014
Last Verified: March 2004
Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
adult solid tumor
body system/site cancer
bone metastases
cellular diagnosis, prostate cancer
genetic condition
male reproductive cancer
metastatic cancer
prostate cancer
recurrent prostate cancer
site, metastatic cancer
solid tumor
stage IV prostate cancer
stage, prostate cancer
unclassified/other cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Neoplasm Metastasis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Bone Density Conservation Agents