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
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Prostatic Neoplasms
Castrate-resistant Prostate Cancer (CRPC)
Androgen-insensitive Prostate Cancer
Hormone-refractory Prostate Cancer
Metastatic Disease
Drug: Itraconazole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Itraconazole in Castrate-resistant Prostate Cancer Post-chemotherapy

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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


Enrollment: 4
Study Start Date: September 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Itraconazole
600 mg/day oral (PO)
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01450683

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Dr. Sandy Srinivas Stanford University
  More Information

No publications provided

Responsible Party: Sandy Srinivas, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01450683     History of Changes
Other Study ID Numbers: IRB-19413, SU-12032010-7271, PROS0037
Study First Received: September 30, 2011
Results First Received: August 29, 2014
Last Updated: August 29, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasm Metastasis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014