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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
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE April 23, 2009
First Posted Date  ICMJE April 24, 2009
Results First Submitted Date  ICMJE December 11, 2013
Results First Posted Date  ICMJE January 27, 2014
Last Update Posted Date October 16, 2017
Study Start Date  ICMJE July 2009
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 28, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
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: To determine the proportion of patients without new/progressive metastases at 24 weeks, as demonstrated on CT and/or bone scan. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2017)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
To Determine the Proportion of Men With ≥ 50% PSA Reduction From Baseline. [ Time Frame: approximately 2 years from open enrollment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy
Official Title  ICMJE A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer
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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Itraconazole 200 mg
    Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
  • Drug: Itraconazole 300mg
    Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Study Arms  ICMJE
  • Active Comparator: Low Dose
    Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
    Intervention: Drug: Itraconazole 200 mg
  • Active Comparator: High Dose
    Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
    Intervention: Drug: Itraconazole 300mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 11, 2013)
46
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2009)
58
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00887458
Other Study ID Numbers  ICMJE J0932
JHMI-IRB number: NA_00027099
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Memorial Sloan Kettering Cancer Center
Investigators  ICMJE
Principal Investigator: Michael A Carducci, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Johns Hopkins University
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP