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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

This study has been completed.
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Michael A. Carducci, MD, Johns Hopkins University Identifier:
First received: April 23, 2009
Last updated: January 28, 2014
Last verified: January 2014

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 Intervention Phase
Prostate Cancer
Drug: Itraconazole 200 mg
Drug: Itraconazole 300mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Michael A. Carducci, MD, Johns Hopkins University:

Primary Outcome Measures:
  • 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:
  • To Determine the Proportion of Men With ≥ 50% PSA Reduction From Baseline. [ Time Frame: approximately 2 years from open enrollment ]

Enrollment: 46
Study Start Date: July 2009
Study Completion Date: December 2013
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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. We 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
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Please refer to this study by its identifier: NCT00887458

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
Principal Investigator: Michael A Carducci, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Responsible Party: Michael A. Carducci, MD, Professor of Urology and Oncology, Johns Hopkins University Identifier: NCT00887458     History of Changes
Other Study ID Numbers: J0932
JHMI-IRB number: NA_00027099
Study First Received: April 23, 2009
Results First Received: December 11, 2013
Last Updated: January 28, 2014

Keywords provided by Michael A. Carducci, MD, Johns Hopkins University:
metastatic prostate cancer
castration resistant prostate cancer
rising PSA

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
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 processed this record on May 25, 2017