Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Dexamethasone

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Dexamethasone acetate

Ketoconazole

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Cytochrome P-450 CYP3A Inhibitors

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.

* 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.

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% 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.

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.

Terence Friedlander, MD

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.

Ketoconazole and Dexamethasone in Prostate Cancer

An Endocrinologically and Pharmacologically Directed Trial of Ketoconazole and Corticosteroids in Castration Resistant Prostate Cancer

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.

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.

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

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.

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.

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.

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.

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.

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.

University of California, San Francisco

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 + Hydrocortisone

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.

Ketoconazole + Dexamethasone

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.

All Patients Who Received Treatment

50-59 years old

60-69 years old

70-79 years old

80-89 years old

Age, Customized

50-59 years

60-69 years

70-79 years

This measure presents data for the 9 participants that were subsequently randomized to the second treatment arm

Sex: Female, Male

Ethnicity (NIH/OMB)

This measure presents data for the participants that were subsequently randomized to the second treatment arm

Race (NIH/OMB)

United States

Region of Enrollment

This is a sequential treatment design. Participants enrolled in first treatment regimen (Ketoconazole + Hydrocortisone) continued on 1st regimen based on disease status at week 12 evaluation and progression status. At progression, a second treatment option was assigned based on response to 1st regimen. 9 of the 32 total were assigned to 2nd regimen

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

Dr. Terence Friedlander, MD

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

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

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

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

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

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

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

Change in Testosterone Levels Over Time for Participants on Dexamethasone

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

Change in Estrodiol Levels Over Time for Participants on Dexamethasone

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

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

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

Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time

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

Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time

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

Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time

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.

Spots Global Cancer Trial Database for Ketoconazole and Dexamethasone in Prostate Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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