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Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy

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ClinicalTrials.gov Identifier: NCT01450683
Recruitment Status : Terminated (Low accrual)
First Posted : October 12, 2011
Results First Posted : September 8, 2014
Last Update Posted : April 11, 2017
Sponsor:
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University

Tracking Information
First Submitted Date  ICMJE September 30, 2011
First Posted Date  ICMJE October 12, 2011
Results First Submitted Date  ICMJE August 29, 2014
Results First Posted Date  ICMJE September 8, 2014
Last Update Posted Date April 11, 2017
Study Start Date  ICMJE September 2010
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2014)
Reduction in Serum PSA [ Time Frame: 12 weeks treatment, with primary outcome assessed at 15 weeks ]
Number of subjects with > 50% drop in serum PSA as compared to baseline, at 12 weeks and confirmed at 15 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2011)
Serum PSA measured after 12 weeks is the study endpoint. If after 10 patients <2 have a response, the study will be halted. [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT01450683 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
Official Title  ICMJE A Phase 2 Study of Itraconazole in Castrate-resistant Prostate Cancer Post-chemotherapy
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Prostatic Neoplasms
  • Castrate-resistant Prostate Cancer (CRPC)
  • Androgen-insensitive Prostate Cancer
  • Hormone-refractory Prostate Cancer
  • Metastatic Disease
Intervention  ICMJE Drug: Itraconazole

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

Other Names:
  • Sporanox
  • R51211
Study Arms  ICMJE Experimental: Itraconazole
600 mg/day oral (PO)
Intervention: Drug: Itraconazole
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 Terminated
Actual Enrollment  ICMJE
 (submitted: July 17, 2012)
4
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2011)
27
Actual Study Completion Date  ICMJE April 2011
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 NCT01450683
Other Study ID Numbers  ICMJE IRB-19413
SU-12032010-7271 ( Other Identifier: Stanford University )
PROS0037 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sandy Srinivas, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dr. Sandy Srinivas Stanford University
PRS Account Stanford University
Verification Date March 2017

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