A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy

NCT ID: NCT00887458

Last Updated: 2017-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-12-31

Brief Summary

This research is being done to test an investigational drug, called itraconazole, in the treatment of prostate cancer. Itraconazole is approved by the Food and Drug Administration (FDA) for the treatment of various fungal infections such as fingernail/toenail infections and other more serious fungal infections. The word "investigational" means that itraconazole is not approved for use in people with cancer. However, the FDA is allowing the use of itraconazole in this research study. Itraconazole has been shown to have activity against cancer (including prostate cancer) in the laboratory, but has not been tested against cancer in humans.

The purpose of this study is to find out:

• If itraconazole is safe when given at two different doses
• How itraconazole affects prostate specific antigen (PSA): a blood test that measures substances released by prostate cancer
• Whether itraconazole can delay further prostate cancer growth and spread
• How itraconazole affects other markers of prostate cancer

Detailed Description

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. The investigators 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.

Conditions

Prostate Cancer

Keywords

metastatic prostate cancer; castration resistant prostate cancer; rising PSA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose

Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)

Group Type: ACTIVE_COMPARATOR

Itraconazole 200 mg

Intervention Type: DRUG

Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)

High Dose

Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)

Group Type: ACTIVE_COMPARATOR

Itraconazole 300mg

Intervention Type: DRUG

Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)

Interventions

Itraconazole 200 mg

Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)

Intervention Type: DRUG

Itraconazole 300mg

Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael A Carducci, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

JHMI-IRB number: NA_00027099

Identifier Type: -

Identifier Source: secondary_id

J0932

Identifier Type: -

Identifier Source: org_study_id