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Trial record 1 of 1 for:    NCT00887458
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A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy

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ClinicalTrials.gov Identifier: NCT00887458
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : January 27, 2014
Last Update Posted : October 16, 2017
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

This research is being done to test an investigational drug, called itraconazole, in the treatment of prostate cancer. Itraconazole is approved by the Food and Drug Administration (FDA) for the treatment of various fungal infections such as fingernail/toenail infections and other more serious fungal infections. The word "investigational" means that itraconazole is not approved for use in people with cancer. However, the FDA is allowing the use of itraconazole in this research study. Itraconazole has been shown to have activity against cancer (including prostate cancer) in the laboratory, but has not been tested against cancer in humans.

The purpose of this study is to find out:

  • If itraconazole is safe when given at two different doses
  • How itraconazole affects prostate specific antigen (PSA): a blood test that measures substances released by prostate cancer
  • Whether itraconazole can delay further prostate cancer growth and spread
  • How itraconazole affects other markers of prostate cancer

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Itraconazole 200 mg Drug: Itraconazole 300mg Phase 2

Detailed Description:

Itraconazole is an oral, generic, and commercially available antifungal drug with a long safety record when used at doses ranging from 200 to 600 mg daily.

Itraconazole has been shown in cellular and animal models to be a potent angiogenesis inhibitor as well as a Hedgehog pathway antagonist; both pathways are considered important in prostate cancer. Itraconazole has not previously been tested as an antineoplastic agent, but given its well-established safety profile, the gap between further preclinical studies and human clinical trials can be narrowed to accelerate development of this agent as a putative anticancer drug. The investigators hypothesize that itraconazole will prevent PSA progression in a significant proportion of men with metastatic CRPC and that it will have an acceptable safety profile at both doses. Itraconazole may ultimately delay the need for chemotherapy in these men.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer
Study Start Date : July 2009
Actual Primary Completion Date : May 2011
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Low Dose
Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
Drug: Itraconazole 200 mg
Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)

Active Comparator: High Dose
Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Drug: Itraconazole 300mg
Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)

Primary Outcome Measures :
  1. To Determine the Proportion of Patients With Metastatic CRPC Who do Not Have Prostate Specific Antigen (PSA) Progression After 24 Weeks of Therapy With One of Two Dose-levels of Itraconazole: 200 mg or 600 mg Daily. [ Time Frame: Up to 24 weeks ]
    To Determine the Proportion of Patients With Metastatic CRPC Who do Not Have Prostate Specific Antigen (PSA) Progression After 24 Weeks of Therapy. "PSA progression" is defined as a 25% increase in PSA over baseline [or nadir (lowest)] and an increase in absolute PSA level by at least 2 ng/mL, both confirmed by a second value at least 4 weeks later.

Secondary Outcome Measures :
  1. To Determine the Proportion of Men With ≥ 50% PSA Reduction From Baseline. [ Time Frame: Baseline and approximately 2 years from open enrollment ]
    Will be reported as the percentage of men with ≥ 50% PSA reduction from baseline.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed prostate adenocarcinoma.
  • Presence of distant metastases on bone scan, CT scan, or MRI scan.
  • Progression after androgen deprivation (and anti-androgen withdrawal).
  • Rising serum PSA (Prostate Cancer Working Group (PCWG2) definition).
  • Castrate levels of serum testosterone (i.e., ≤ 50 ng/dL).
  • Age > 18 years.
  • ECOG performance status score ≤ 2, and/or Karnofsky score ≥ 50%.
  • Life expectancy > 6 months.
  • Adequate kidney, liver, and bone marrow function.
  • Willingness to sign informed consent and adhere to study requirements.

Exclusion Criteria:

  • Recent surgery, radiation therapy, combined androgen blockade, or investigational therapies in the last 8 weeks.
  • Previous chemotherapy for metastatic prostate cancer.
  • Concomitant use of second-line hormonal agents (e.g., ketoconazole, DES)
  • Current use of corticosteroids, except if on a stable dose for ≥ 3 months.
  • History of malabsorption syndrome (may affect itraconazole absorption).
  • Allergic reactions to itraconazole or similar compounds.
  • Concurrent use of drugs that interact with the CYP3A4 system (caution only).
  • Presence of known brain metastases.
  • Prior malignancy in the last 3 years, with some exceptions.
  • Uncontrolled major infectious, cardiac, or pulmonary illnesses.
  • Prolonged corrected QT interval (> 450 msec) on electrocardiography.

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 ClinicalTrials.gov identifier (NCT number): NCT00887458

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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Johns Hopkins University
Memorial Sloan Kettering Cancer Center
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Principal Investigator: Michael A Carducci, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00887458    
Other Study ID Numbers: J0932
JHMI-IRB number: NA_00027099
First Posted: April 24, 2009    Key Record Dates
Results First Posted: January 27, 2014
Last Update Posted: October 16, 2017
Last Verified: September 2017
Keywords provided by Johns Hopkins University:
metastatic prostate cancer
castration resistant prostate cancer
rising PSA
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
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