Keto/Dex: Ketoconazole and Dexamethasone in Prostate Cancer

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01036594
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 57.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is an open label, phase II, single center trial of ketoconazole/dexamethasone to determine if the administration of ketoconazole/dexamethasone, after disease progression with ketoconazole/hydrocortisone slows or reverses disease progression in men with progressive prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Ketoconazole; Drug: Hydrocortisone; Drug: Dexamethasone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Endocrinologically and Pharmacologically Directed Trial of Ketoconazole and Corticosteroids in Castration Resistant Prostate Cancer
• Actual Study Start Date: Dec 11, 2009
• Actual Primary Completion Date: Dec 11, 2012
• Actual Study Completion Date: Oct 9, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketoconazole + Hydrocortisone po = oral tid = 3 times per day qam = every morning qom = every evening bid = twice daily 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If participant has ≥ 30% Prostate-specific antigen (PSA) decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by Prostate Specific Antigen Working Group (PSAWG) criteria) is documented. After that, drug will be discontinued. If participant has < 30% PSA decline at 12 week evaluation, participant goes off study.	Drug: Ketoconazole; 200mg during first week of study (run-in phase), then 400mg po tid; Other Names: Ketoconazole Oral ; Drug: Hydrocortisone; Hydrocortisone 20mg po qam and 10mg po qpm If participant has ≥30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If participant has <30% PSA decline, patient goes off study.
Experimental: Ketoconazole + Dexamethasone Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression (by RECIST criteria OR by PSAWG criteria) is documented.	Drug: Ketoconazole; 200mg during first week of study (run-in phase), then 400mg po tid; Other Names: Ketoconazole Oral ; Drug: Dexamethasone; Dexamethasone 0.5mg po bid If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression (by RECIST criteria OR by PSAWG criteria) is documented.; Other Names: Dexamethasone Oral

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen [Up to 5 years]

   The number of participants who experience a ≥30% decline in PSA between the time of first progression on ketoconazole and hydrocortisone and eight weeks after dexamethasone therapy was initiated.

Secondary Outcome Measures

1. Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone [Up to 5 years]

   Nonparametric Wilcoxon test for matched pairs will be used to test the difference in ACTH levels from baseline until the time of disease progression for participants taking ketoconazole/hydrocortisone for participants with evaluable laboratory values.

2. Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response [Up to 2 years]

   The Spearman rank correlation will be calculated to explore the relationship between the baseline ACTH level and the duration of castration prior to the start of any ketoconazole therapy

3. Change in Testosterone Levels Over Time for Participants on Dexamethasone [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of testosterone levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in testosterone from progression #1 to progression #2.

4. Change in Estrodiol Levels Over Time for Participants on Dexamethasone [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of estrodiol levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in estrodiol from progression #1 to progression #2.

5. Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of AA levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in AA levels from progression #1 to progression #2.

6. Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of cortisol levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in cortisol levels from progression #1 to progression #2.

7. Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of DHEA levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in DHEA levels from progression #1 to progression #2.

8. Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time [Up to 5 years]

   For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of DHEA-S levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in DHEA-S levels from progression #1 to progression #2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate.

• Testosterone < 50 ng/dL. Participants must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy.

• Progressive non-metastatic or metastatic disease after androgen deprivation.

Participants must have EITHER:

1. Progression as defined by RECIST criteria. OR

2. Progressive PSA documented within 4 weeks of enrollment. PSA evidence for progressive prostate cancer consists of a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the first documented rising PSA value, then an additional test for rising PSA will be required to document progression.

• Participants who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen.

1. Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression.

2. For participants receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.

3. For participants receiving bicalutamide (Casodex) or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation.

• Karnofsky Performance Status ≥ 60%.

• Participants receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrollment.

• Participants on stable doses of bisphosphonates may continue on this medication; further, patients may initiate bisphosphonate therapy at the time of ketoconazole initiation.

• Prior radiation therapy completed ≥ 4 weeks prior to enrollment.

• Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Bilirubin) must be within normal limits.

• Absolute Neutrophil Count (ANC) >1500/µl, Platelet count > 100,00/µl, Creatinine <1.5 x upper limit of normal (ULN), Hemoglobin > 8 mg/dl.

Exclusion Criteria:

• Prior chemotherapy for prostate cancer is not allowed with the exception of cases in which chemotherapy has been administered in a neoadjuvant or adjuvant fashion AND >1 year has elapsed since the administration of this therapy.

• No prior ketoconazole, abiraterone, aminoglutethimide or corticosteroids for treatment of progressive prostate cancer.

• No supplements or complementary medicines/botanicals are permitted while on protocol therapy, except for any combination of the following: (conventional multivitamin supplements, selenium, lycopene, soy supplements) No prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.

• No "currently active" second malignancy, other than non-melanoma skin cancer.

• No serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled.

• No psychiatric illnesses/social situations that would limit compliance

• No active or uncontrolled autoimmune disease.

• No adrenal insufficiency as demonstrated by a baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol >18 µg/dL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94115

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Terence Friedlander, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01036594
• Other Study ID Numbers: 09553; NCI-2011-01263
• First Posted: Dec 21, 2009
• Last Update Posted: Jun 29, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by University of California, San Francisco: Ketoconazole; Dexamethasone
• Additional relevant MeSH terms: Prostatic Neoplasms; Ketoconazole; Dexamethasone; Dexamethasone acetate; Hydrocortisone; BB 1101

Study Results

Participant Flow

Recruitment Details	Participants were recruited through the Urologic Oncology Program at University of California, San Francisco
Pre-assignment Detail	All participants were prescribed ketoconazole for a 7 day run-in phase, then hydrocortisone + ketoconazole treatment. Participants not achieving >=30% PSA decline at 12 weeks were taken off study. Participants continued treatment until progression at which time, hydrocortisone was discontinued and ketoconazole + dexamethasone treatment began.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during run-in phase, then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If participant has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by Prostate Specific Antigen Working Group (PSAWG) criteria) is documented. After that, drug will be discontinued. If participant has < 30% PSA decline at 12 week evaluation, participant goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Period Title: Run-In: Ketoconazole Only (200 mg)
STARTED	32	0
COMPLETED	31	0
NOT COMPLETED	1	0
Period Title: Run-In: Ketoconazole Only (200 mg)
STARTED	31	0
COMPLETED	30	0
NOT COMPLETED	1	0
Period Title: Run-In: Ketoconazole Only (200 mg)
STARTED	30	0
COMPLETED	24	0
NOT COMPLETED	6	0
Period Title: Run-In: Ketoconazole Only (200 mg)
STARTED	15	9
COMPLETED	13	5
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	All Patients Who Received Treatment
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If participant has < 30% PSA decline at 12 week evaluation, participant goes off study. Based on the results of evaluation at 12 weeks , participants were offered to either stay on this regimen or receive -Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Overall Participants	32
Age, Customized (Count of Participants)
50-59 years old	7 21.9%
60-69 years old	11 34.4%
70-79 years old	10 31.3%
80-89 years old	4 12.5%
Age, Customized (Count of Participants)
50-59 years	1 3.1%
60-69 years	6 18.8%
70-79 years	2 6.3%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	32 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%
Not Hispanic or Latino	27 84.4%
Unknown or Not Reported	3 9.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%
Not Hispanic or Latino	6 18.8%
Unknown or Not Reported	1 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 9.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 6.3%
White	26 81.3%
More than one race	0 0%
Unknown or Not Reported	1 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 9.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.1%
White	5 15.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen
Description	The number of participants who experience a ≥30% decline in PSA between the time of first progression on ketoconazole and hydrocortisone and eight weeks after dexamethasone therapy was initiated.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Progression data for patients not enrolled to Dexamethasone arm are not used in this analysis.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	8
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone
Description	Nonparametric Wilcoxon test for matched pairs will be used to test the difference in ACTH levels from baseline until the time of disease progression for participants taking ketoconazole/hydrocortisone for participants with evaluable laboratory values.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

ACTH data not collected for this endpoint. Planned statistical analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

3. Secondary Outcome

Title	Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response
Description	The Spearman rank correlation will be calculated to explore the relationship between the baseline ACTH level and the duration of castration prior to the start of any ketoconazole therapy
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Data on duration of castration prior to treatment data not collected. Planned analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

4. Secondary Outcome

Title	Change in Testosterone Levels Over Time for Participants on Dexamethasone
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of testosterone levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in testosterone from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Testosterone data for this endpoint not collected. Planned statistical analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

5. Secondary Outcome

Title	Change in Estrodiol Levels Over Time for Participants on Dexamethasone
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of estrodiol levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in estrodiol from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Estrodiol data for this endpoint not collected. Planned statistical analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

6. Secondary Outcome

Title	Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of AA levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in AA levels from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

AA data not collected for this endpoint. Planned statistical analyses could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

7. Secondary Outcome

Title	Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of cortisol levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in cortisol levels from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Cortisol data not collected for this endpoint. Planned statistical analysis could not be performed

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

8. Secondary Outcome

Title	Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of DHEA levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in DHEA levels from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

DHEA data was not collected for this endpoint. Planned statistical analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

9. Secondary Outcome

Title	Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time
Description	For PSA responders to ketoconazole/ hydrocortisone continuing with dexamethasone treatment after initial disease progression, the overall pattern of DHEA-S levels will be investigated with nonparametric methods for statistical analyses. This will include Friedman's analysis of variance method using ranks for repeated measures. A key comparison using the Wilcoxon test for matched pairs will investigate the change in DHEA-S levels from progression #1 to progression #2.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

DHEA-S data was not collected for this endpoint. Planned statistical analysis could not be performed.

Arm/Group Title	Ketoconazole + Hydrocortisone	Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.	Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 5 years
Arm/Group Title	Ketoconazole + Hydrocortisone		Ketoconazole + Dexamethasone
Arm/Group Description	po = oral, tid = 3 times per day, qam = every morning, qom = every evening, bid = twice daily, 1 cycle = 28 days Ketoconazole: 200mg during first week of study (run-in phase), then 400mg po tid Hydrocortisone 20mg po qam and 10mg po qpm: If patient has ≥ 30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If patient has < 30% PSA decline at 12 week evaluation, patient goes off study.		Ketoconazole: 400mg po tid Dexamethasone 0.5mg po bid: If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.
All Cause Mortality
	Ketoconazole + Hydrocortisone		Ketoconazole + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/9 (0%)
Serious Adverse Events
	Ketoconazole + Hydrocortisone		Ketoconazole + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/32 (12.5%)		0/9 (0%)
Gastrointestinal disorders
Dehydration	1/32 (3.1%)	1	0/9 (0%)	0
Infections and infestations
Infection with unknown ANC - Bladder (urinary)	1/32 (3.1%)	1	0/9 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	1/32 (3.1%)	1	0/9 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)	1/32 (3.1%)	1	0/9 (0%)	0
Infection - Other	1/32 (3.1%)	1	0/9 (0%)	0
Musculoskeletal and connective tissue disorders
Fracture	1/32 (3.1%)	1	0/9 (0%)	0
Renal and urinary disorders
Renal failure	1/32 (3.1%)	2	0/9 (0%)	0
Obstruction, GU - Ureter	1/32 (3.1%)	1	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/32 (3.1%)	1	0/9 (0%)	0
Vascular disorders
Peripheral arterial ischemia	1/32 (3.1%)	2	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Ketoconazole + Hydrocortisone		Ketoconazole + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/32 (78.1%)		5/9 (55.6%)
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]	0/32 (0%)	0	1/9 (11.1%)	1
Cardiac disorders
Cardiac Arrhythmia - Other	2/32 (6.3%)	3	0/9 (0%)	0
Supraventricular and nodal arrhythmia - Sinus bradycardia	2/32 (6.3%)	3	0/9 (0%)	0
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)	2/32 (6.3%)	2	2/9 (22.2%)	2
Gastrointestinal disorders
Nausea	6/32 (18.8%)	9	1/9 (11.1%)	1
Constipation	3/32 (9.4%)	3	1/9 (11.1%)	1
Anorexia	2/32 (6.3%)	2	0/9 (0%)	0
Diarrhea	3/32 (9.4%)	3	0/9 (0%)	0
Dry mouth/salivary gland (xerostomia)	3/32 (9.4%)	3	0/9 (0%)	0
Vomiting	3/32 (9.4%)	3	0/9 (0%)	0
Taste alteration (dysgeusia)	1/32 (3.1%)	1	1/9 (11.1%)	1
Hemorrhoids	0/32 (0%)	0	1/9 (11.1%)	1
Mucositis/stomatitis (clinical exam) - Oral cavity	0/32 (0%)	0	1/9 (11.1%)	1
Abdomen Pain, NOS	4/32 (12.5%)	8	0/9 (0%)	0
General disorders
Fatigue (asthenia, lethargy, malaise)	12/32 (37.5%)	23	2/9 (22.2%)	2
Insomnia	2/32 (6.3%)	3	1/9 (11.1%)	1
Weight gain	1/32 (3.1%)	1	1/9 (11.1%)	2
Weight loss	1/32 (3.1%)	1	1/9 (11.1%)	2
Edema: limb	7/32 (21.9%)	14	2/9 (22.2%)	2
Pain - Other	3/32 (9.4%)	3	0/9 (0%)	0
Pain - Chest/thorax NOS	2/32 (6.3%)	3	0/9 (0%)	0
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other	0/32 (0%)	0	1/9 (11.1%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	1/32 (3.1%)	1	1/9 (11.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	0/32 (0%)	0	1/9 (11.1%)	1
Infection with unknown ANC - Joint	0/32 (0%)	0	1/9 (11.1%)	1
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) increased	5/32 (15.6%)	15	1/9 (11.1%)	1
AST, SGOT(serum glutamic oxaloacetic transaminase) increased	6/32 (18.8%)	9	0/9 (0%)	0
Creatinine increased	2/32 (6.3%)	3	0/9 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	2/32 (6.3%)	2	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Pain - Back	3/32 (9.4%)	4	0/9 (0%)	0
Pain - Extremity-limb	3/32 (9.4%)	4	0/9 (0%)	0
Pain - Joint	2/32 (6.3%)	2	1/9 (11.1%)	2
Fracture	2/32 (6.3%)	2	1/9 (11.1%)	2
Joint-effusion	0/32 (0%)	0	1/9 (11.1%)	1
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	0/32 (0%)	0	1/9 (11.1%)	1
Osteoporosis	0/32 (0%)	0	1/9 (11.1%)	1
Nervous system disorders
Cognitive disturbance	2/32 (6.3%)	2	0/9 (0%)	0
Syncope (fainting)	2/32 (6.3%)	2	0/9 (0%)	0
Psychiatric disorders
Mood alteration - Depression	2/32 (6.3%)	2	2/9 (22.2%)	2
Renal and urinary disorders
Urinary frequency/urgency	5/32 (15.6%)	6	0/9 (0%)	0
Renal/Genitourinary	2/32 (6.3%)	3	1/9 (11.1%)	1
Perforation, GU - Kidney	0/32 (0%)	0	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	4/32 (12.5%)	8	0/9 (0%)	0
Bronchospasm, wheezing	1/32 (3.1%)	1	1/9 (11.1%)	1
Cough	1/32 (3.1%)	2	1/9 (11.1%)	1
Pneumonitis/pulmonary infiltrates	0/32 (0%)	0	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Dermatology - Other	8/32 (25%)	17	1/9 (11.1%)	1
Dry skin	8/32 (25%)	13	0/9 (0%)	0
Rash/desquamation	3/32 (9.4%)	4	0/9 (0%)	0
Rash: hand-foot skin reaction	3/32 (9.4%)	3	1/9 (11.1%)	1
Rash: dermatitis associated with radiation - Radiation	0/32 (0%)	0	1/9 (11.1%)	1
Vascular disorders
Hypertension	5/32 (15.6%)	11	0/9 (0%)	0
Peripheral arterial ischemia	2/32 (6.3%)	2	0/9 (0%)	0

Limitations/Caveats

Sample size and data collection for evaluable endpoints insufficient to complete planned analyses

More Information

Certain Agreements

All Principal Investigators ARE 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.