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

Sponsor:	Johns Hopkins University
Collaborator:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00887458

Purpose

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

Condition	Intervention	Phase
Prostate Cancer	Drug: Itraconazole 200 mg Drug: Itraconazole 300mg	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Phase II Clinical Trial of Two Dose-levels of Itraconazole in Patients With Metastatic Castration-resistant Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Itraconazole

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

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. [ Time Frame: To determine the proportion of patients without new/progressive metastases at 24 weeks, as demonstrated on CT and/or bone scan. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the proportion of men with ≥ 50% PSA reduction from baseline. [ Time Frame: approximately 2 years from open enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment:	58
Study Start Date:	July 2009

Arms	Assigned Interventions
Low Dose: Active Comparator Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)	Drug: Itraconazole 200 mg Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose)
High Dose: Active Comparator Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)	Drug: Itraconazole 300mg Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)

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. 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887458

Contacts

Contact: Serina King

410-614-6139

sking18@jhmi.edu

Locations

United States, Maryland
Johns Hopkins Hospital	Recruiting
Baltimore, Maryland, United States, 21231
Contact: Serina King 410-614-6139 sking18@jhmi.edu
Contact: Rana Sullivan, RN 410-614-6337 tomalra@jhmi.edu
Principal Investigator: Michael Carducci, MD
Sub-Investigator: Emmanuel S Antonarakis, MD
United States, Michigan
Karmanos Cancer Center	Recruiting
Detroit, Michigan, United States, 48201
Contact: Brenda Dickow, RN 313-576-9372 dickowb@karmanos.org
Contact: Kimberlee Dobson 313-576-9837 dobsonk@karmanos.org
Principal Investigator: Elizabeth Heath, MD
University of Michigan Comprehensive Cancer Center	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Tamara Huebner, RN 734-763-4992 thuebner@umich.edu
Principal Investigator: David C. Smith, MD
United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Sara Wise 646-227-2127 wises@mskcc.org
Principal Investigator: Dana Rathkopf, MD

Sponsors and Collaborators

Johns Hopkins University

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Michael A Carducci, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

No publications provided

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Michael Carducci, MD )
Study ID Numbers:	J0932, JHMI-IRB number: NA_00027099
Study First Received:	April 23, 2009
Last Updated:	January 12, 2010
ClinicalTrials.gov Identifier:	NCT00887458 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Johns Hopkins University:

metastatic prostate cancer
castration resistant prostate cancer
rising PSA

Additional relevant MeSH terms:

Itraconazole
Hydroxyitraconazole
Anti-Infective Agents
Antiprotozoal Agents
Genital Neoplasms, Male
Prostatic Diseases
Urogenital Neoplasms
Genital Diseases, Male

Pharmacologic Actions
Antiparasitic Agents
Neoplasms
Neoplasms by Site
Antifungal Agents
Therapeutic Uses
Prostatic Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010