Clinical trial NCT01036594: Ketoconazole and Dexamethasone in Prostate Cancer
Official title: An Endocrinologically and Pharmacologically Directed Trial of Ketoconazole and Corticosteroids in Castration Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Ketoconazole
Dexamethasone
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2009-12-21
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen
timeFrame: Up to 5 years
Secondary outcomes:
measure: Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone
timeFrame: Up to 5 years
measure: Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response
timeFrame: Up to 2 years
measure: Change in Testosterone Levels Over Time for Participants on Dexamethasone
timeFrame: Up to 5 years
measure: Change in Estrodiol Levels Over Time for Participants on Dexamethasone
timeFrame: Up to 5 years
measure: Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time
timeFrame: Up to 5 years
measure: Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time
timeFrame: Up to 5 years
measure: Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time
timeFrame: Up to 5 years
measure: Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Terence Friedlander, MD
role: PRINCIPAL_INVESTIGATOR
References: