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.
Sponsor:
Collaborator:
Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):
Michael A. Carducci, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00887458
First received: April 23, 2009
Last updated: January 28, 2014
Last verified: January 2014

April 23, 2009
January 28, 2014
July 2009
May 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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.
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. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00887458 on ClinicalTrials.gov Archive Site
To Determine the Proportion of Men With ≥ 50% PSA Reduction From Baseline. [ Time Frame: approximately 2 years from open enrollment ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy
A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • 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)
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
December 2013
May 2011   (final data collection date for primary outcome measure)

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.
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00887458
J0932, JHMI-IRB number: NA_00027099
Yes
Michael A. Carducci, MD, Johns Hopkins University
Johns Hopkins University
Memorial Sloan-Kettering Cancer Center
Principal Investigator: Michael A Carducci, MD Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University
January 2014

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