Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
Primary Purpose
Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Itraconazole
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
INCLUSION CRITERIA
- Male aged ≥ 18 years
- Life expectancy ≥ 6 months
- Histologically- or cytologically-confirmed adenocarcinoma of the prostate
- Metastatic disease or prior history of metastases, as documented by positive bone scan or metastatic lesions on CT or MRI
- Prostate cancer progression, as documented by PSA according to PCWG2 or radiographic progression according to RECIST criteria version 1.1
- Progression must have been during or after docetaxel based chemotherapy.
- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is currently being treated with LHRH agonists (patient who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and treatment must be continued throughout the study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Hemoglobin ≥ 10.0 g/dL
- Platelet count ≥100,000 microliters
- Serum creatinine ≤ 2, OR a calculated creatinine clearance ≥ 40 mL/min
- Serum bilirubin < 1.5 x ULN (except for patients Gilbert's disease)
- AST or ALT < 2.5 x ULN
- Able to swallow the study drug whole as a tablet
- Willing and able to provide written informed consent
EXCLUSION CRITERIA
- Known brain metastasis
- Radiation therapy within 4 weeks of Cycle 1, Day 1
- Prior systemic treatment with an azole drug (eg, fluconazole, ketoconazole) within 4 weeks of Cycle 1, Day 1
- Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for ≥ 3 months months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1,Day 1)
- Prior Bicalutamide (Casodex), nilutamide (Nilandron) treatment within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for ≥ 3 months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1 Day 1)
- Known active or symptomatic viral hepatitis or chronic liver disease
- Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic events in the past 6 months; severe or unstable angina
- Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
- Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
- Any condition which, in the opinion of the investigator, would preclude the patient's participation in this trial.
- No more than 3 prior chemotherapy regimens.
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Itraconazole
Arm Description
600 mg/day oral (PO)
Outcomes
Primary Outcome Measures
Reduction in Serum PSA
Number of subjects with > 50% drop in serum PSA as compared to baseline, at 12 weeks and confirmed at 15 weeks
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01450683
Brief Title
Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
Official Title
A Phase 2 Study of Itraconazole in Castrate-resistant Prostate Cancer Post-chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
September 2010 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study evaluates if itraconazole causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC).
Detailed Description
Castration-resistant prostate cancer (CRPC) is also known as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in the setting of CRPC, there remains unmet medical need, largely expressed as the lack of durable response. New therapies that extend survival of patients beyond that provided by chemotherapy are needed.
It is hypothesized that the triazole antifungal drug itraconazole, through its activity as a potent inhibitor of the Hedgehog (Hh) signaling pathway via the Smoothened (Smo) pathway, may provide clinical benefit in the treatment of prostate cancer. The Hh signaling pathway is a critical embryonic developmental pathway whose aberrant activity has been implicated in the growth and metastases of a variety of tumor types including prostate cancer. Itraconazole is structurally related to ketoconazole, demonstrated to reduce serum PSA by more than 50% in about 20 to 25% of treated prostate cancer subjects.
This study will assess efficacy on the basis of serum levels of PSA, an established surrogate endpoint for efficacy in prostate cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC), Androgen-insensitive Prostate Cancer, Hormone-refractory Prostate Cancer, Metastatic Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Itraconazole
Arm Type
Experimental
Arm Description
600 mg/day oral (PO)
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Other Intervention Name(s)
Sporanox, R51211
Intervention Description
600 mg/day oral (PO)
IUPAC name: (2R,4S)-rel-1-(Butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
Primary Outcome Measure Information:
Title
Reduction in Serum PSA
Description
Number of subjects with > 50% drop in serum PSA as compared to baseline, at 12 weeks and confirmed at 15 weeks
Time Frame
12 weeks treatment, with primary outcome assessed at 15 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA
Male aged ≥ 18 years
Life expectancy ≥ 6 months
Histologically- or cytologically-confirmed adenocarcinoma of the prostate
Metastatic disease or prior history of metastases, as documented by positive bone scan or metastatic lesions on CT or MRI
Prostate cancer progression, as documented by PSA according to PCWG2 or radiographic progression according to RECIST criteria version 1.1
Progression must have been during or after docetaxel based chemotherapy.
Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is currently being treated with LHRH agonists (patient who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and treatment must be continued throughout the study.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
Hemoglobin ≥ 10.0 g/dL
Platelet count ≥100,000 microliters
Serum creatinine ≤ 2, OR a calculated creatinine clearance ≥ 40 mL/min
Serum bilirubin < 1.5 x ULN (except for patients Gilbert's disease)
AST or ALT < 2.5 x ULN
Able to swallow the study drug whole as a tablet
Willing and able to provide written informed consent
EXCLUSION CRITERIA
Known brain metastasis
Radiation therapy within 4 weeks of Cycle 1, Day 1
Prior systemic treatment with an azole drug (eg, fluconazole, ketoconazole) within 4 weeks of Cycle 1, Day 1
Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for ≥ 3 months months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1,Day 1)
Prior Bicalutamide (Casodex), nilutamide (Nilandron) treatment within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for ≥ 3 months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1 Day 1)
Known active or symptomatic viral hepatitis or chronic liver disease
Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic events in the past 6 months; severe or unstable angina
Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
Any condition which, in the opinion of the investigator, would preclude the patient's participation in this trial.
No more than 3 prior chemotherapy regimens.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Sandy Srinivas
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
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