Ketoconazole and Dexamethasone in Prostate Cancer | NCT01036594

NCT01036594

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
NCI-2011-01263	Registry Identifier	NCI Clinical Trials Reporting Program (CTRP)

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ketoconazole + Hydrocortisone	Experimental	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 Drug: Hydrocortisone
Ketoconazole + Dexamethasone	Experimental	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 Drug: Dexamethasone

Name	Type	Description	Arm Group Labels	Other Names
Ketoconazole	Drug	200mg during first week of study (run-in phase), then 400mg po tid	Ketoconazole + Dexamethasone Ketoconazole + Hydrocortisone

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen	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.	Up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone	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.	Up to 5 years

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Terence Friedlander, MD	University of California, San Francisco	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Francisco		San Francisco	California	94115	United States

Arm/Group Information

ID	Title	Description
FG000	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 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.
FG001	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 on Ketoconazole + Hydrocortisone (by RECIST criteria OR by PSAWG criteria) is documented.

Periods

Title

Milestones

Reasons Not Completed

Run-In: Ketoconazole Only (200 mg)

Type	Comment	Milestone Data
STARTED		FG00032 subjects FG0010 subjectsDexamethasone not introduced as treatment option until after Week 12 evaluation
COMPLETED		FG00031 subjects FG0010 subjects
NOT COMPLETED		FG0001 subjects FG0010 subjects

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0010 subjects

First Treatment Regimen

Type	Comment	Milestone Data
STARTED		FG00031 subjects FG0010 subjectsDexamethasone not introduced as treatment option until after Week 12 evaluation
COMPLETED		FG00030 subjects

Week 12 Evaluation

Type	Comment	Milestone Data
STARTED		FG00030 subjects FG0010 subjectsDexamethasone not introduced as treatment option until after Week 12 evaluation
COMPLETED		FG00024 subjects

Treatment Regiments Post Week 12

Type	Comment	Milestone Data
STARTED		FG00015 subjects FG0019 subjects
COMPLETED		FG00013 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Patients Who Received Treatment	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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen

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.

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

Posted

Count of Participants

Participants

Up to 5 years

ID	Title	Description
OG000	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 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 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.

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011282	Pregnenediones

ID	Term
D007654	Ketoconazole
D006854	Hydrocortisone
D003907	Dexamethasone