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”

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.

- 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.

Intervention(s) in this Clinical Trial

• Drug: Ketaconazole
  • 200mg orally three times a day on an empty stomach.
• Drug: Hydrocortisone
  • 30mg in the morning and 10mg in the evening. Pills should be taken with food or milk.
• Drug: Dutasteride
  • 0.5mg orally once a day on an empty stomach or after eating a meal.

Primary Measures

• To evaluate the efficacy of high dose ketoconazole and hydrocortisone in combination with dutasteride (KHAD) in the treatment of hormone refractory prostate cancer.
  • Time Frame: TBD
    Safety Issue?: No

Secondary Measures

• To evaluate the toxicity of the combination in hormone refractory prostate cancer.
  • Time Frame: 2 years
    Safety Issue?: Yes
• To evaluate the time to progression on KHAD.
  • Time Frame: TBD
    Safety Issue?: No
• Correlate levels of androgens and metabolites with response.
  • Time Frame: TBD
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Beth Israel Deaconess Medical Center Other

Overall Clinical Trial Officials and Contacts

Steven Balk, MD Principal Investigator Beth Israel Deaconess Medical Center  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00673127

Study ID Number: 04-414

ClinicalTrials.gov Identifier: NCT00673127

Health Authority: United States: Food and Drug Administration