Oral Calcitriol With Ketoconazole in CRPC

• Sponsor: Donald Trump, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03261336
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 13.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The aim of this study is to estimate the PSA response rate with the use of ketoconazole (400mg QD + hydrocortisone 20mg AM, 10 mg PM) among men with CRPC in whom disease has progressed despite abiraterone

Condition or Disease	Intervention/Treatment	Phase
Castration-resistant Prostate Cancer	Drug: Calcitriol, Ketoconazole, Hydrocortisone	Phase 2

Detailed Description

This study will aim to describe objective tumor responses to the combination of oral calcitriol and ketoconazole and hydrocortisone-among patients with measurable disease using modified RECIST 1.1 criteria.

Additionally, we will determine toxicities, and tolerability of oral calcitriol combination with daily oral ketoconazole, and hydrocortisone in this patient population.

this is a single arm phase II trial of ketoconazole (400mg QD + hydrocortisone 20mg AM, 10 mg PM) among men with CRPC in whom disease has progressed despite abiraterone

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Calcitriol 10mcg QD X3, weekly + Ketoconazole 400mg po TID and Hydrocortisone 20mg AM, 10mg PMCalcitriol 10mcg QD X3, weekly + Ketoconazole 400mg po TID and Hydrocortisone 20mg AM, 10mg PM
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone
• Actual Study Start Date: Jan 6, 2017
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Calcitriol, Ketoconazole, Hydrocortisone Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).	Drug: Calcitriol, Ketoconazole, Hydrocortisone; Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol; Other Names: Rocaltrol® active form of vitamin D3

Outcome Measures

Primary Outcome Measures

1. PSA Response Rate [2 years]

   Assessment of PSA every 4 weeks

Secondary Outcome Measures

1. Tumor Response [2 years]

   Objective tumor response among patients with measurable disease using modified RECIST1.1

2. Toxicity and Tolerability of Experimental Arm [2 years]

   Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

For inclusion in the trial, a patient must fulfill all of the following criteria:

1. Greater than or equal to 18 years of age. The effects of ketoconazole and high-dose calcitriol have not been studied adequately in patients <18 years of age and prostate cancer has not been described in children.

2. Histologically or cytologically confirmed adenocarcinoma consistent clinically with androgen Independent prostate cancer

3. Measurable disease with elevated PSA or evaluable disease (PSA elevation will constitute evaluable disease).

4. No cytotoxic chemotherapy for extensive disease prior to study entry will be allowed; given the recent data regarding the role of docetaxel + ADT in patients beginning ADT for advanced disease, such "adjuvant chemotherapy will be allowed (no more than 6 cycles) retinoids, vitamin D analogues, PPAR agonists or antagonists, antiandrogens, progestational agents, estrogens, PC-SPES, LHRH analogues, vaccines, cytokines will not be considered "cytotoxics." Patients who have previously received ketoconazole + glucocorticoids will NOT be eligible for this trial.

5. Patients who have received antiandrogens or progestational agents as therapy for prostate cancer must discontinue therapy and demonstrate a rising PSA > 28 days following discontinuation (antiandrogen withdrawal - AAW) (>42 days for bicalutamide or nilutamide). Patients who receive megestrol acetate as therapy for "hot flashes" at a dose of <40mg per day may continue this therapy during this trial. The dose of the megestrol acetate should not be changed during protocol treatment. Patients undergoing androgen deprivation using LHRH analogues must continue such agents or undergo orchiectomy to maintain castrate levels of testosterone.

6. Patients must have prostate cancer that is advanced or recurrent.

7. Patients should not have received any chemotherapy or investigational agents for at least 28 days before entering the study.

8. Eastern Clinical Oncology Group performance status 0 or 1

9. Life expectancy >3 months.

10. Patients must have normal organ and marrow function as defined below:

leukocytes: >3,000/μl hemoglobin: > 8 g/dl absolute neutrophil count (ANC):>1,500/μl platelets: >75,000/μl total bilirubin: within normal institutional limit AST/ALT: <2.5 X institutional upper limit of normal creatinine: < 2mg/dL calcium: not above normal institutional limit

1. Patients should be able to receive oral medications.

2. Patients with brain metastases which are stable and have been treated with surgery and/or irradiation will be eligible for this trial.

3. The effects of high-dose calcitriol and ketoconazole on the developing human fetus are unknown. For this reason and because these agents as well are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform the treating physician immediately.

4. Ability to understand and the willingness to sign a written informed consent document.

5. Progressive disease must have occurred on abiraterone within the prior 12 months and patient must not have received treatment with enzalutamide.

Men of all ethnic groups are eligible for this trial. Efforts will be made to include minority groups and all representative ethnicities and races in the community.

Exclusion Criteria

Any of the following is a criterion for exclusion from the trial:

1. Known severe hypersensitivity to ketoconazole, calcitriol or any of the excipients of these products.

2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to calcitriol, ketoconazole, or other agents used in study.

3. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial.

4. History of kidney, ureteral, or bladder stones within the last 5 years

5. Heart failure or significant heart disease including significant arrhythmias, myocardial infarction within the last 3 months, unstable angina, documented ejection fraction <30%, or current digoxin therapy.

6. Thiazide therapy within 7 days from entering the study.

7. Requirement for concurrent systemic glucocorticoid therapy at greater than physiologic replacement doses

8. Unwillingness to stop calcium supplementation.

9. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) or intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

10. Human immunodeficiency virus-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible PK interactions with ketoconazole or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

11. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's wort, alfentanil, alfuzosin, almotriptan, alprazolam, amiodarone, amitriptyline, amprenavir, aprepitant, aripiprazole, bepridil, bortezomib, bosentan, budesonide, buprenorphine, buspirone, carbamazepine, cilostazol, cisapride, cyclosporine, delavirdine, didanosine, digoxin, disopyramidedofetilide, donepezil, eletriptan, eplerenone, fluticasone, fosamprenavir, galantamine, systemic griseofulvin, indinavir, levobupivacaine, lopinavir, midazolam, mifepristone, modafinil, nateglinide, nefazadone, nelfinavir, oxcarbazepine, pimozide, quetiapine, quinidine, repaglinide, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, sildenafil, sirolimus, tacrolimus, tadalafil, tolterodine, theophyllines, tolterodine, triazolam, valdecoxib, vardenafil, ziprasidone, zonisamide, statins, with the exception of pravastatin (Pravachol) or other "statins" which are not metabolized by or induce CYP3A4, calcium channel blockers, and macrolides or other agents that will be significantly perturbed in a clinically important way by the P450 inhibitory properties of ketoconazole

12. Concomitant use of proton pump inhibitors or H2 blockers

13. Treatment with a non-approved or investigational drug or agent within 28 days before day 1 of trial treatment.

14. Any unresolved chronic toxicity greater then CTC Grade 2 from previous anticancer therapy.

15. Incomplete healing from previous oncologic treatments or other major surgery.

16. Inability to swallow oral capsules.

17. Patients on digoxin will be excluded from this study.

Products Dosage and Mode of Administration

• Ketoconazole, 200 mg tablets, 2 tablets orally TID

• Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week

• Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

• Donald Trump, MD

Investigators

• Principal Investigator: Skip (Donald) Trump, MD, CEO & Executive Director Inova Schar Cancer Institute

Study Documents (Full-Text)

• Informed Consent Form - Sep 11, 2017
• Study Protocol and Statistical Analysis Plan - Jul 10, 2017

More Information

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• Responsible Party: Donald Trump, MD, CEO & Executive Director, Inova Schar Cancer Institute, Inova Health Care Services
• ClinicalTrials.gov Identifier: NCT03261336
• Other Study ID Numbers: 16-2200
• First Posted: Aug 25, 2017
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Vitamin D; Calcitriol; Ketoconazole; Hydrocortisone

Study Results

Participant Flow

Recruitment Details	Study was closed at site in 2018 due to enrollment challenges. Only 1 patient was enrolled to trial. No evaluable results.

Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	1 100%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	78
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	PSA Response Rate
Description	Assessment of PSA every 4 weeks
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Only one patient enrolled to study and was discontinued early due to AE.

Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
Measure Participants	0

2. Secondary Outcome

Title	Tumor Response
Description	Objective tumor response among patients with measurable disease using modified RECIST1.1
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Only one patient was enrolled and was discontinued due to AE.

Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
Measure Participants	0

3. Secondary Outcome

Title	Toxicity and Tolerability of Experimental Arm
Description	Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patient developed hypercalcemia and was discontinued from study. AE is known, not unexpected.

Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
Measure Participants	1
Count of Participants [Participants]	1 100%

Adverse Events

Time Frame	AE data was collected on a single patient during one month in 2017.
Adverse Event Reporting Description	Definition consistent with clinicaltrials.gov
Arm/Group Title	Calcitriol, Ketoconazole, Hydrocortisone
Arm/Group Description	Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM). Calcitriol, Ketoconazole, Hydrocortisone: Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week Ketoconazole, 200 mg tablets, 2 tablets orally TID Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose of Calcitriol
All Cause Mortality
	Calcitriol, Ketoconazole, Hydrocortisone
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Calcitriol, Ketoconazole, Hydrocortisone
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
hypercalcemia	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Calcitriol, Ketoconazole, Hydrocortisone
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

Study was closed due to inability to accrue. One patient was entered on study and did develop hypercalcemia which led to treatment discontinuation. Insufficient time on study to evaluate response.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.