Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ketoconazole, Hydrocortisone and Dutasteride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KHAD<br>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 | Drug: Ketoconazole, Hydrocortisone and Dutasteride<br>* 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<br>* Other names: Dutasteride=Avodart;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response | PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later. | From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Duration of time from treatment initiation until documented progression (PSA or Disease progression) | Duration of time from treatment initiation until documented progression. Maximum 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone refractory, KHAD, ketoconazole, dutasteride, hydrocortisone