Ketoconazole and Dexamethasone in Prostate Cancer

NCT ID: NCT01036594

Last Updated: 2020-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-11
• Study Completion Date: 2014-10-09

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ketoconazole

Intervention Type: DRUG

200mg during first week of study (run-in phase), then 400mg po tid

Hydrocortisone

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Ketoconazole

Intervention Type: DRUG

200mg during first week of study (run-in phase), then 400mg po tid

Dexamethasone

Intervention Type: DRUG

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.

Interventions

Ketoconazole

200mg during first week of study (run-in phase), then 400mg po tid

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Ketoconazole Oral; Dexamethasone Oral

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Terence Friedlander, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Other Identifiers

NCI-2011-01263

Identifier Type: REGISTRY

Identifier Source: secondary_id

09553

Identifier Type: -

Identifier Source: org_study_id