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

This study has been terminated.
(Low accrual)
Sponsor:
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier:
NCT01450683
First received: September 30, 2011
Last updated: August 29, 2014
Last verified: August 2014

September 30, 2011
August 29, 2014
September 2010
April 2011   (final data collection date for primary outcome measure)
Reduction in Serum PSA [ Time Frame: 12 weeks treatment, with primary outcome assessed at 15 weeks ] [ Designated as safety issue: No ]
Number of subjects with > 50% drop in serum PSA as compared to baseline, at 12 weeks and confirmed at 15 weeks
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 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01450683 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
A Phase 2 Study of Itraconazole in Castrate-resistant Prostate Cancer Post-chemotherapy

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).

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prostate Cancer
  • Prostatic Neoplasms
  • Castrate-resistant Prostate Cancer (CRPC)
  • Androgen-insensitive Prostate Cancer
  • Hormone-refractory Prostate Cancer
  • Metastatic Disease
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:
  • Itraconazole
  • Sporanox
  • R51211
Experimental: Itraconazole
600 mg/day oral (PO)
Intervention: Drug: Itraconazole
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
April 2011
April 2011   (final data collection date for primary outcome measure)

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.
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01450683
IRB-19413, SU-12032010-7271, PROS0037
Yes
Sandy Srinivas, Stanford University
Stanford University
Not Provided
Principal Investigator: Dr. Sandy Srinivas Stanford University
Stanford University
August 2014

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