Ketoconazole and Dexamethasone in Prostate Cancer

NCT01036594 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 09553NCI-2011-01263
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Keywords

Ketoconazole; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• 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 (8)

• Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone

  Up to 5 years

• Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response

  Up to 2 years

• Change in Testosterone Levels Over Time for Participants on Dexamethasone

  Up to 5 years

• Change in Estrodiol Levels Over Time for Participants on Dexamethasone

  Up to 5 years

• Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time

  Up to 5 years

Study Arms (2)

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

Interventions

Ketoconazole DRUG

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

Also known as: Ketoconazole Oral

Ketoconazole + Dexamethasone; Ketoconazole + Hydrocortisone

Hydrocortisone 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 + Hydrocortisone

Dexamethasone 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.

Also known as: Dexamethasone Oral

Ketoconazole + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Progression as defined by RECIST criteria. OR
• 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.
• 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.
• For participants receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ketoconazole; Hydrocortisone; Dexamethasone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Terence Friedlander, MD
• Organization: University of California, San Francisco

Terence.Friedlander@ucsf.edu

(415) 514-6380

Study Officials

• Terence Friedlander, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 21, 2009
• Study Start: December 11, 2009
• Primary Completion: December 11, 2012
• Study Completion: October 9, 2014
• Last Updated: June 29, 2020
• Results First Posted: June 29, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)