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A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer

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. We 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.

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Description:

To determine the proportion of patients without new/progressive metastases at 24 weeks, as demonstrated on CT and/or bone scan.

Outcome Time Frame:

Up to 24 weeks

Safety Issue:


Principal Investigator

Michael A Carducci, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2009

Completion Date:

Related Keywords:

  • Prostate Cancer
  • metastatic prostate cancer
  • castration resistant prostate cancer
  • rising PSA
  • Prostatic Neoplasms
  • Disease Progression



Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Johns Hopkins Hospital Baltimore, Maryland  21287
Karmanos Cancer Center Detroit, Michigan  48201