Prostate CancerPhase 2Keto/DexNCT01036594

Ketoconazole and Dexamethasone in Prostate Cancer

A Phase 2 study testing Ketoconazole, Hydrocortisone and Dexamethasone in people with Prostate Cancer, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Prostate Cancer
What is being tested?: Ketoconazole, Hydrocortisone and Dexamethasone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 11 Dec 2009to 9 Oct 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California, San Francisco
San Francisco, California, 94115

Other trials in United States

About this study

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

Conditions: Prostate Cancer
Being tested: Ketoconazole, Hydrocortisone, Dexamethasone
Keywords: Ketoconazole, Dexamethasone
Medical subject headings: Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetoconazoleDrug
Also called Ketoconazole Oral
200mg during first week of study (run-in phase), then 400mg po tid
HydrocortisoneDrug
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.
DexamethasoneDrug
Also called Dexamethasone Oral
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.

Study groups in NCT01036594
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Ketoconazole; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 5 years

Secondary outcomes (8)

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.
Measured: Up to 5 years
Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response
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
Measured: Up to 2 years
Change in Testosterone Levels Over Time for Participants on Dexamethasone
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.
Measured: Up to 5 years
Change in Estrodiol Levels Over Time for Participants on Dexamethasone
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.
Measured: Up to 5 years
Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time
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.
Measured: Up to 5 years
Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time
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.
Measured: Up to 5 years
Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time
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.
Measured: Up to 5 years
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time
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.
Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Dec 20099 Oct 2014

First posted21 Dec 2009 (estimated)
Study start11 Dec 2009
Primary completion11 Dec 2012
Study completion9 Oct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Prostate CancerStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01036594
Sponsor's protocol ID: 09553
Other IDs: NCI-2011-01263
Acronym: Keto/Dex
Status last verified: Jun 2020
First submitted: 17 Dec 2009
Last updated: 29 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Endocrinologically and Pharmacologically Directed Trial of Ketoconazole and Corticosteroids in Castration Resistant Prostate Cancer
ClinicalTrials.gov ID: NCT01036594
Acronym / sponsor ID: Keto/Dex / 09553
Conditions: Prostate Cancer
Keywords: Ketoconazole, Dexamethasone
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Study start: 11 Dec 2009 (actual)
Primary completion: 11 Dec 2012 (actual)
Study completion: 9 Oct 2014 (actual)
First posted: 21 Dec 2009 (estimated)
Results: Posted 29 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Ketoconazole + Hydrocortisone	Experimental	Drug: Ketoconazole, Drug: Hydrocortisonepo = 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 + Dexamethasone	Experimental	Drug: Ketoconazole, Drug: 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.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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:
Participants who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen.
Karnofsky Performance Status ≥ 60%.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KetoconazoleAlso: Ketoconazole Oral200mg during first week of study (run-in phase), then 400mg po tid	Drug	Ketoconazole + Dexamethasone, Ketoconazole + Hydrocortisone
HydrocortisoneHydrocortisone 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.	Drug	Ketoconazole + Hydrocortisone
DexamethasoneAlso: Dexamethasone OralDexamethasone 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 + Dexamethasone

Primary outcome

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

8 secondary outcomes

Median Change Over Time in Adrenocorticotrophic Hormone (ACTH) Levels for Participants Taking Ketoconazole/Hydrocortisone
Time frame: Up to 5 years
Relationship of ACTH to the Duration of Castration Prior to Treatment With Ketoconazole/Hydrocortisone and With Response
Time frame: Up to 2 years
Change in Testosterone Levels Over Time for Participants on Dexamethasone
Time frame: Up to 5 years
Change in Estrodiol Levels Over Time for Participants on Dexamethasone
Time frame: Up to 5 years
Change in Serum Adrenal Androgen (AA) Levels Over Time for Participants on Dexamethasone Over Time
Time frame: Up to 5 years
Change in Cortisol Levels Over Time for Participants on Dexamethasone Over Time
Time frame: Up to 5 years
Change in Dehydroepiandrosterone (DHEA) Levels Over Time for Participants on Dexamethasone Over Time
Time frame: Up to 5 years
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Levels Over Time for Participants on Dexamethasone Over Time
Time frame: Up to 5 years

Results and safety

Results posted to the registry on 29 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketoconazole + Hydrocortisone	32	31
Ketoconazole + Dexamethasone	0	0

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

Time frame: Up to 5 years. Count of participants. Unit: Participants

Measure	Ketoconazole + Hydrocortisone n = 0	Ketoconazole + Dexamethasone n = 8
Value	–	0

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

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 5 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketoconazole + Hydrocortisone	4 of 32 (12.5%)	25 of 32 (78.1%)	0 of 32
Ketoconazole + Dexamethasone	0 of 9 (0%)	5 of 9 (55.6%)	0 of 9

Limitations and caveats (from the sponsor): Sample size and data collection for evaluable endpoints insufficient to complete planned analyses

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Terence Friedlander, MD principal investigator

University of California, San Francisco

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketoconazole, Hydrocortisone and Dexamethasone in people with Prostate Cancer, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Achieved a Second Decline in Prostate Specific Antigen (PSA) Following Progression on First Regimen (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01036594.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2020.