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

This study has been completed.
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Steven Balk, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00673127
First received: May 5, 2008
Last updated: December 27, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Ketaconazole
Drug: Hydrocortisone
Drug: Dutasteride
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the toxicity of the combination in hormone refractory prostate cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To evaluate the time to progression on KHAD. [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • Correlate levels of androgens and metabolites with response. [ Time Frame: TBD ] [ Designated as safety issue: No ]

Enrollment: 57
Study Start Date: February 2005
Study Completion Date: December 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KHAD
KHAD
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673127

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at John Hopkins University
Baltimore, Maryland, United States
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States
Canada
Sunnybrook and Women's College Health Sciences Center
Toronto, Canada
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
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
Investigators
Principal Investigator: Steven Balk, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Steven Balk, MD, Principle Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00673127     History of Changes
Other Study ID Numbers: 04-414
Study First Received: May 5, 2008
Last Updated: December 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
hormone refractory
KHAD
ketoconazole
dutasteride
hydrocortisone

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Cortisol succinate
Dutasteride
Hormones
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Ketoconazole
14-alpha Demethylase Inhibitors
5-alpha Reductase Inhibitors
Anti-Infective Agents
Anti-Inflammatory Agents
Antifungal Agents
Dermatologic Agents
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Urological Agents

ClinicalTrials.gov processed this record on October 23, 2014