Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer (KHAD)

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Ketoconazole, Hydrocortisone and Dutasteride

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Sunnybrook and Women's College Health Sciences Center
• United States
  • Maryland
    • Baltimore, Maryland, United States
      • Sidney Kimmel Comprehensive Cancer Center at John Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health and Science University
  • Texas
    • Houston, Texas, United States
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KHAD; 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; 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; Other Names: Dutasteride=Avodart

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: M.D. Anderson Cancer Center; Massachusetts General Hospital; Sunnybrook Health Sciences Centre; Dana-Farber Cancer Institute; Oregon Health and Science University; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Steven Balk, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 5, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimate): May 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: hydrocortisone; dutasteride; hormone refractory; KHAD; ketoconazole
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; 5-alpha Reductase Inhibitors; Ketoconazole; Hydrocortisone; Dutasteride
• Other Study ID Numbers: 04-414