Prostate Cancer
Conditions
Keywords
hormone refractory, KHAD, ketoconazole, dutasteride, hydrocortisone
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.
Interventions
DRUGKetoconazole, Hydrocortisone and Dutasteride
Ketoconazole: 200mg orally three times a day on an empty stomach. Hydrocortisone: 30mg in the morning and 10mg in the evening. Pills should be taken with food or milk. Dutasteride: 0.5mg orally once a day on an empty stomach or after eating a meal
Sponsors
Massachusetts General Hospital
Dana-Farber Cancer Institute
Sunnybrook Health Sciences Centre
Oregon Health and Science University
M.D. Anderson Cancer Center
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Canada, United States
Participant flow
Recruitment details
Medical oncology clinics
Pre-assignment details
Required 6 week washout for any AR antagonists
Participants by arm
| Arm | Count |
|---|---|
| KHAD Ketoconazole, Hydrocortisone and Dutasteride | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | KHAD |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 7 |
| Region of Enrollment Canada | 8 participants |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 57 |
| serious Total, serious adverse events | 1 / 57 |
Outcome results
Primary
PSA Response
PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later.
Time frame: From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KHAD | PSA Response | 56 percentage of participants |
Secondary
Time to Progression
Duration of time from treatment initiation until documented progression (PSA or Disease progression)
Time frame: Duration of time from treatment initiation until documented progression. Maximum 32 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| KHAD | Time to Progression | 14.5 months |