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

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00673127
• Collaborator: Massachusetts General Hospital (Other), Dana-Farber Cancer Institute (Other), Sunnybrook Health Sciences Centre (Other), Oregon Health and Science University (Other), M.D. Anderson Cancer Center (Other), Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Enrollment: 57
• Locations: 7
• Arm: 1
• Duration (Months): 94
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Ketoconazole, Hydrocortisone and Dutasteride	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. PSA Response [From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months.]

   PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later.

Secondary Outcome Measures

1. Time to Progression [Duration of time from treatment initiation until documented progression. Maximum 32 months]

   Duration of time from treatment initiation until documented progression (PSA or Disease progression)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at John Hopkins University	Baltimore	Maryland	United States
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
5	Oregon Health and Science University	Portland	Oregon	United States
6	MD Anderson Cancer Center	Houston	Texas	United States
7	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 at Johns Hopkins

Investigators

• Principal Investigator: Steven Balk, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steven Balk, MD, Principle Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00673127
• Other Study ID Numbers: 04-414
• First Posted: May 7, 2008
• Last Update Posted: Apr 22, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Steven Balk, MD, Principle Investigator, Dana-Farber Cancer Institute: hormone refractory; KHAD; ketoconazole; dutasteride; hydrocortisone
• Additional relevant MeSH terms: Prostatic Neoplasms; Ketoconazole; Hydrocortisone; Dutasteride

Study Results

Participant Flow

Recruitment Details	Medical oncology clinics
Pre-assignment Detail	Required 6 week washout for any AR antagonists

Arm/Group Title	KHAD
Arm/Group Description	KHAD; ketoconazole, hydrocortisone and dutasteride for CRPC
Period Title: Overall Study
STARTED	57
COMPLETED	57
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	KHAD
Arm/Group Description	Ketoconazole, Hydrocortisone and Dutasteride
Overall Participants	57
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 56.1%
>=65 years	25 43.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (7)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	57 100%
Region of Enrollment (participants) [Number]
United States	49 86%
Canada	8 14%

Outcome Measures

1. Primary Outcome

Title	PSA Response
Description	PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later.
Time Frame	From treatment initiation until treatment cessation. Maximum 32 months. Median treament duration 8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KHAD
Arm/Group Description	Ketoconazole, Hydrocortisone and Dutasteride
Measure Participants	57
Number (95% Confidence Interval) [percentage of participants]	56 98.2%

2. Secondary Outcome

Title	Time to Progression
Description	Duration of time from treatment initiation until documented progression (PSA or Disease progression)
Time Frame	Duration of time from treatment initiation until documented progression. Maximum 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KHAD
Arm/Group Description	KHAD: ketoconazole, hydrocortisone and dutasteride for CRPC
Measure Participants	57
Median (95% Confidence Interval) [months]	14.5

Adverse Events

Arm/Group Title	KHAD
Arm/Group Description	Ketoconazole, Hydrocortisone and Dutasteride
All Cause Mortality
	KHAD
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	KHAD
	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)
Vascular disorders
grade 4 thrombosis	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	KHAD
	Affected / at Risk (%)	# Events
Total	56/57 (98.2%)
Blood and lymphatic system disorders
Hemoglobin	23/57 (40.4%)
Hematologic-other	1/57 (1.8%)
Cardiac disorders
Cardiomyopathy, restrictive	1/57 (1.8%)
Cardiac-other	1/57 (1.8%)
Ear and labyrinth disorders
Tinnitus	1/57 (1.8%)
Endocrine disorders
Endocrine-other	1/57 (1.8%)
Eye disorders
Cataract	1/57 (1.8%)
Dry eye syndrome	3/57 (5.3%)
Vision-blurred	2/57 (3.5%)
Tearing	1/57 (1.8%)
Ocular-other	2/57 (3.5%)
Gastrointestinal disorders
Constipation	5/57 (8.8%)
Diarrhea w/o prior colostomy	4/57 (7%)
Distention/bloating, abdominal	1/57 (1.8%)
Dry mouth	4/57 (7%)
Esophagitis	1/57 (1.8%)
Flatulence	1/57 (1.8%)
Gastritis	1/57 (1.8%)
Dyspepsia	6/57 (10.5%)
Incontinence, anal	1/57 (1.8%)
Nausea	14/57 (24.6%)
Vomiting	4/57 (7%)
GI-other	5/57 (8.8%)
General disorders
Fatigue	21/57 (36.8%)
Fever w/o neutropenia	1/57 (1.8%)
Constitutional, other	6/57 (10.5%)
Edema head and neck	1/57 (1.8%)
Edema limb	10/57 (17.5%)
Pain-other	5/57 (8.8%)
Infections and infestations
Infection Gr0-2 neut, sinus	1/57 (1.8%)
Infection-other	1/57 (1.8%)
Injury, poisoning and procedural complications
Bruising	2/57 (3.5%)
Investigations
Lymphopenia	3/57 (5.3%)
Weight gain	2/57 (3.5%)
Alkaline phosphatase	6/57 (10.5%)
ALT, SGPT	27/57 (47.4%)
AST, SGOT	29/57 (50.9%)
Bilirubin	3/57 (5.3%)
Creatinine	15/57 (26.3%)
Metabolic/Laboratory-other	2/57 (3.5%)
Metabolism and nutrition disorders
Pancreatic glucose intolerance	1/57 (1.8%)
Hypoalbuminemia	1/57 (1.8%)
Hypocalcemia	1/57 (1.8%)
Hyperglycemia	21/57 (36.8%)
Hypoglycemia	4/57 (7%)
Hypomagnesemia	1/57 (1.8%)
Hyperkalemia	2/57 (3.5%)
Hypokalemia	6/57 (10.5%)
Hyponatremia	1/57 (1.8%)
Hyperuricemia	2/57 (3.5%)
Musculoskeletal and connective tissue disorders
Nonneuropathic lower extr muscle weak	2/57 (3.5%)
Nonneuropathic generalized weakness	1/57 (1.8%)
Back, pain	1/57 (1.8%)
Extremity-limb, pain	1/57 (1.8%)
Nervous system disorders
Taste disturbance	6/57 (10.5%)
Cognitive disturbance	1/57 (1.8%)
Dizziness	2/57 (3.5%)
Memory impairment	1/57 (1.8%)
Neuropathy-sensory	1/57 (1.8%)
Neurologic-other	3/57 (5.3%)
Head/headache	4/57 (7%)
Psychiatric disorders
Insomnia	5/57 (8.8%)
Agitation	3/57 (5.3%)
Anxiety	1/57 (1.8%)
Depression	3/57 (5.3%)
Personality	1/57 (1.8%)
Renal and urinary disorders
Cystitis	1/57 (1.8%)
Incontinence urinary	2/57 (3.5%)
Urinary frequency/urgency	6/57 (10.5%)
Urinary retention	1/57 (1.8%)
Reproductive system and breast disorders
Erectile impotence	2/57 (3.5%)
Gynecomastia	2/57 (3.5%)
Respiratory, thoracic and mediastinal disorders
Nose, hemorrhage	3/57 (5.3%)
Cough	2/57 (3.5%)
Dyspnea	4/57 (7%)
Nasal cavity/paranasal sinus reaction	3/57 (5.3%)
Voice changes/dysarthria	1/57 (1.8%)
Pulmonary/Upper Respiratory-other	1/57 (1.8%)
Skin and subcutaneous tissue disorders
Sweating	2/57 (3.5%)
Dry skin	9/57 (15.8%)
Alopecia	2/57 (3.5%)
Hyperpigmentation	1/57 (1.8%)
Nail changes	5/57 (8.8%)
Pruritus/itching	1/57 (1.8%)
Rash/desquamation	8/57 (14%)
Rash: acne/acneiform	1/57 (1.8%)
Skin-other	7/57 (12.3%)
Vascular disorders
Hypertension	12/57 (21.1%)
Hypotension	1/57 (1.8%)
Flushing	1/57 (1.8%)
Hot flashes	10/57 (17.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.