Clinical trial NCT00673127: Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer
Official title: A Phase II Trial of Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: hormone refractory
KHAD
ketoconazole
dutasteride
hydrocortisone
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: Dana-Farber Cancer Institute
name: Sunnybrook Health Sciences Centre
name: Oregon Health and Science University
name: M.D. Anderson Cancer Center
name: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
First posted: 2008-05-07
Enrollment: 57
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: PSA Response
timeFrame: From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months.
Secondary outcomes:
measure: Time to Progression
timeFrame: Duration of time from treatment initiation until documented progression. Maximum 32 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Sunnybrook and Women's College Health Sciences Center
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Steven Balk, MD
role: PRINCIPAL_INVESTIGATOR
References: