Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

Condition(s) targeted: Prostate Cancer

Intervention: Ketoconazole, Hydrocortisone and Dutasteride (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Beth Israel Deaconess Medical Center

Official(s) and/or principal investigator(s):
Steven Balk, MD, Principal Investigator, Affiliation: Beth Israel Deaconess Medical Center

The combination of ketaconazole and hydrocortisone is commonly used for the treatment of prostate cancer. The purpose of this study is to determine if the addition of a drug called dutasteride to this approved combination will make the combination more effective in treating prostate cancer.

Official title: A Phase II Trial of Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: PSA Response

Secondary outcome: Time to Progression

Detailed description:

- Participants will be seen by the study physician every four weeks and have a short

physical examination, blood tests and be asked to provide information about their condition. Every three months they will undergo a bone scan. If the CT scan that was obtained before the participant started the study shows evidence of cancer, they will be asked to repeat this test every three months.

- Ketaconazole will be taken orally three times a day on an empty stomach.

Hydrocortisone will be taken orally in the morning and at night. Dutasteride will be taken orally once a day.

- Participants may remain on study drug until there is evidence of disease progression.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Histologically documented evidence of prostate cancer (needle biopsy or

prostatectomy). In the abscence of histologically documented evidence of prostate cancer, the diagnosis must be based on elevated serum PSA and metastatic lesions on bone scan.

- Progressive HRPC defined as a PSA increase over baseline of >25% or 5ng/ml or new

lesions on bone/CT scan after conventional androgen deprivation and antiandrogen withdrawal. Evidence of metastatic disease based on positive CT or bone scan is not required.

- PSA of greater than or equal to 2ng/ml and serum total testosterone less than or

equal to 50ng/ml

- Prior chemotherapy is permitted if discontinued > 4 weeks prior to starting therapy

- Prior therapy with estrogens is permitted but must have been discontinued > 4 weeks

prior to registration

- ECOG Performance Status 0-2

- Adequate renal function, hepatic function, and bone marrow function as outlined in

protocol

- ECG showing a normal QT interval

Exclusion Criteria:

- Prior therapy with ketoconazole or corticosteroids for HRPC

- Major surgery or radiation therapy within 4 weeks

- Strontium-89 or samarium-153 therapy within 4 weeks

- Thromboembolism in past 6 months

- Patients who are taking drugs that may further prolong QT intervals and present a

known risk for Torsades de Pointes.

- Concomitant use of drugs known to be narrow therapeutic index CTP3A4

- Drugs that are sensitive CYP3A4 substrates

- Alcohol or drug dependence currently or in the last 6 months

Sunnybrook and Women's College Health Sciences Center, Toronto, Canada

Sidney Kimmel Comprehensive Cancer Center at John Hopkins University, Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Massachusetts General Hospital, Boston, Massachusetts 02214, United States

Oregon Health and Science University, Portland, Oregon, United States

MD Anderson Cancer Center, Houston, Texas, United States

Starting date: February 2005
Last updated: April 20, 2015