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Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ketoconazole
Hydrocortisone
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring PSA, Ketoconazole, Prostate Cancer, Hormone Refractory, Chemotherapy Regimen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically or cytologically proven prostate cancer with a Gleason score available or interpretable.
  • Patients must have prostate cancer deemed to be hormone refractory, by progression of measurable or evaluable disease or rising PSA.
  • Patients must be >18 years old
  • Patients must have received at least one prior chemotherapy regimen >3 weeks prior to initiation of study and patients must have recovered from the side effects of the therapy
  • Patients must have an ECOG status of 0-3
  • Patients must have normal organ and marrow function, determined within 14 days of registration.
  • Patients must have been surgically or medically castrated. If the method of castration was LHRH agonists (leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists.
  • Patients must have a serum total testosterone level <50 ng/dl
  • If the patient has been treated with non-steroidal anti-androgens (flutamide, bicalutamide or nilutamide) or other hormonal treatment (megace or steroids), the patient must have stopped these agents at least 28 days prior to enrollment for flutamide, megace or steroids and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the patients must have demonstrated progression of disease since the agents were suspended.

Exclusion Criteria:

  • Patients with any condition that impairs the ability to swallow medications orally
  • Patients who are unable to give informed consent
  • Patients who have received ketoconazole treatment for prostate cancer in the past
  • Patients with other active malignancies in the past 3 years except nonmelanoma skin cancer
  • Patients may not be receiving any other investigational agents
  • Patients with known hypersensitivity to ketoconazole
  • Patients may not be taking certain medications, including terbinafine, astemizole, triazolam, statins (except pravastatin and fluvastatin) and acid suppressive agents (antacids, H2 blockers, PPI) while on ketoconazole, and patients on these medications must agree to discontinue these medications and consider alternative therapies.

Sites / Locations

  • University of California, Davis Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketoconazole and Hydrocortisone

Arm Description

Ketoconazole 200mg PO TID + Hydrocortisone 20mg PO Qam, 10mg PO Qpm

Outcomes

Primary Outcome Measures

Prostate Specific Antigen (PSA) Response (>50% Reduction From Baseline)
Percentage of patients who achieved a clinically significant decline in Prostate Specific Antigen (PSA) after initiation of ketoconazole therapy, defined as a >=50% decrease in PSA.

Secondary Outcome Measures

PSA Response (>30% From Baseline)
Progression Free Survival
Response Evaluation Criteria In Solid Tumors (RECIST) radiographic criteria for progression
Duration of Stable Disease

Full Information

First Posted
May 6, 2009
Last Updated
February 28, 2017
Sponsor
University of California, Davis
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1. Study Identification

Unique Protocol Identification Number
NCT00895310
Brief Title
Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy
Official Title
Assessing PSA Response in Low Dose Ketoconazole in Hormone Refractory Prostate Cancer Patients Who Have Failed at Least One Prior Systemic Chemotherapy Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to test the safety of ketoconazole and how well it works after chemotherapy has been used. Ketoconazole at lower doses has been used for fungal infections however has not yet been approved by the Food and Drug Administration for use in prostate cancer. Ketoconazole has been used for many years at high doses for prostate cancer, and this study will be to look at use of lower dose ketoconazole after someone has received chemotherapy. Ketoconazole works by halting the production of steroids in your body, including testosterone, and is thought to work directly on prostate cancer cells in published lab studies.
Detailed Description
The aim of the study is to research the response of low dose ketoconazole in hormone refractory prostate cancer (HRPC) patients who have already undergone chemotherapy as part of their prostate cancer treatment. The hypothesis of the study is that HRPC patients who have been previously treated with chemotherapy will demonstrate objective PSA response rates to low dose ketoconazole, comparable to historical response rates reported in chemotherapy-naïve patients. This is a single arm trial, with all participants given ketoconazole 200mg TID, along with hydrocortisone given at 20mg in the morning, 10mg at night daily. Each cycle will consist of 28 days. The subject's study participation will continue until subject experiences disease progression, unacceptable toxicities, withdraws consent from the study or dies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
PSA, Ketoconazole, Prostate Cancer, Hormone Refractory, Chemotherapy Regimen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketoconazole and Hydrocortisone
Arm Type
Experimental
Arm Description
Ketoconazole 200mg PO TID + Hydrocortisone 20mg PO Qam, 10mg PO Qpm
Intervention Type
Drug
Intervention Name(s)
Ketoconazole
Other Intervention Name(s)
Nizoral
Intervention Description
Ketoconazole is taken three times a day by mouth.
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Other Intervention Name(s)
Cortef
Intervention Description
Hydrocortisone is taken by mouth 20 mg every morning and 10 mg every evening.
Primary Outcome Measure Information:
Title
Prostate Specific Antigen (PSA) Response (>50% Reduction From Baseline)
Description
Percentage of patients who achieved a clinically significant decline in Prostate Specific Antigen (PSA) after initiation of ketoconazole therapy, defined as a >=50% decrease in PSA.
Time Frame
From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years
Secondary Outcome Measure Information:
Title
PSA Response (>30% From Baseline)
Time Frame
From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years
Title
Progression Free Survival
Description
Response Evaluation Criteria In Solid Tumors (RECIST) radiographic criteria for progression
Time Frame
From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years
Title
Duration of Stable Disease
Time Frame
From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically proven prostate cancer with a Gleason score available or interpretable. Patients must have prostate cancer deemed to be hormone refractory, by progression of measurable or evaluable disease or rising PSA. Patients must be >18 years old Patients must have received at least one prior chemotherapy regimen >3 weeks prior to initiation of study and patients must have recovered from the side effects of the therapy Patients must have an ECOG status of 0-3 Patients must have normal organ and marrow function, determined within 14 days of registration. Patients must have been surgically or medically castrated. If the method of castration was LHRH agonists (leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists. Patients must have a serum total testosterone level <50 ng/dl If the patient has been treated with non-steroidal anti-androgens (flutamide, bicalutamide or nilutamide) or other hormonal treatment (megace or steroids), the patient must have stopped these agents at least 28 days prior to enrollment for flutamide, megace or steroids and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the patients must have demonstrated progression of disease since the agents were suspended. Exclusion Criteria: Patients with any condition that impairs the ability to swallow medications orally Patients who are unable to give informed consent Patients who have received ketoconazole treatment for prostate cancer in the past Patients with other active malignancies in the past 3 years except nonmelanoma skin cancer Patients may not be receiving any other investigational agents Patients with known hypersensitivity to ketoconazole Patients may not be taking certain medications, including terbinafine, astemizole, triazolam, statins (except pravastatin and fluvastatin) and acid suppressive agents (antacids, H2 blockers, PPI) while on ketoconazole, and patients on these medications must agree to discontinue these medications and consider alternative therapies.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Primo N Lara Jr., MD
Organizational Affiliation
University of California, Davis Health System
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
25667107
Citation
Lo EN, Beckett LA, Pan CX, Robles D, Suga JM, Sands JM, Lara PN Jr. Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis. 2015 Jun;18(2):144-8. doi: 10.1038/pcan.2015.2. Epub 2015 Feb 10.
Results Reference
result

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Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy

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