Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

Phase 2

Completed

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
KHAD	Ketoconazole, Hydrocortisone and Dutasteride	Ketoconazole, Hydrocortisone and Dutasteride Ketoconazole: 200mg orally three times a day on an empty stomach. Hydrocortisone: 30mg in the morning and 10mg in the evening. Dutasteride: 0.5 mg once a day

Primary Outcome Measures

Name	Time	Method
PSA Response	From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months.	PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	Duration of time from treatment initiation until documented progression. Maximum 32 months	Duration of time from treatment initiation until documented progression (PSA or Disease progression)

Locations (7): Sidney Kimmel Comprehensive Cancer Center at John Hopkins University
🇺🇸
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Sunnybrook and Women's College Health Sciences Center
🇨🇦
Toronto, Canada