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

NCT00895310 | Completed Phase 2 Results DMC

• 2 other identifiers: 200916901UCDCC#218
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

PSA; Ketoconazole; Prostate Cancer; Hormone Refractory; Chemotherapy Regimen

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (3)

• PSA Response (>30% From Baseline)

  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

• Progression Free Survival

  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

• Duration of Stable Disease

  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

Study Arms (1)

Ketoconazole and Hydrocortisone

EXPERIMENTAL

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

Drug: Ketoconazole; Drug: Hydrocortisone

Interventions

Ketoconazole DRUG

Ketoconazole is taken three times a day by mouth.

Also known as: Nizoral

Ketoconazole and Hydrocortisone

Hydrocortisone DRUG

Hydrocortisone is taken by mouth 20 mg every morning and 10 mg every evening.

Also known as: Cortef

Ketoconazole and Hydrocortisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California, Davis Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• 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.

  PMID: 25667107 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ketoconazole; Hydrocortisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Analyst
• Organization: University of California Davis

pkaujla@ucdavis.edu

9167340294

Study Officials

• Primo N Lara Jr., MD

  University of California, Davis Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2009
• First Posted: May 8, 2009
• Study Start: May 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: May 1, 2015
• Last Updated: March 30, 2017
• Results First Posted: February 15, 2017

Record last verified: 2017-02

Locations

US (1)