Back to resultsA Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Itraconazole 200 mg
Itraconazole 300mg
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring metastatic prostate cancer, castration resistant prostate cancer, rising PSA
Eligibility Criteria
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.
Sites / Locations
- Johns Hopkins Hospital
- University of Michigan Comprehensive Cancer Center
- Karmanos Cancer Center
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Low Dose
High Dose
Arm Description
Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Outcomes
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.
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.
Will be reported as the percentage of men with ≥ 50% PSA reduction from baseline.
Full Information
NCT ID
NCT00887458
First Posted
April 23, 2009
Last Updated
September 13, 2017
Sponsor
Johns Hopkins University
Collaborators
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT00887458
Brief Title
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
A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Memorial Sloan Kettering Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
metastatic prostate cancer, castration resistant prostate cancer, rising PSA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose
Arm Type
Active Comparator
Arm Description
Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
Arm Title
High Dose
Arm Type
Active Comparator
Arm Description
Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Intervention Type
Drug
Intervention Name(s)
Itraconazole 200 mg
Intervention Description
Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
Intervention Type
Drug
Intervention Name(s)
Itraconazole 300mg
Intervention Description
Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
To Determine the Proportion of Men With ≥ 50% PSA Reduction From Baseline.
Description
Will be reported as the percentage of men with ≥ 50% PSA reduction from baseline.
Time Frame
Baseline and approximately 2 years from open enrollment
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Carducci, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy
We'll reach out to this number within 24 hrs