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Oral Calcitriol With Ketoconazole in CRPC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03261336
Recruitment Status : Terminated (can not meet enrollment)
First Posted : August 25, 2017
Last Update Posted : March 2, 2018
Information provided by (Responsible Party):
Donald Trump, MD, Inova Health Care Services

Tracking Information
First Submitted Date  ICMJE July 12, 2017
First Posted Date  ICMJE August 25, 2017
Last Update Posted Date March 2, 2018
Actual Study Start Date  ICMJE January 6, 2017
Actual Primary Completion Date February 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 23, 2017)
PSA response rate [ Time Frame: 2 years ]
Assessment of PSA every 4 weeks
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2017)
  • Tumor response [ Time Frame: 2 years ]
    Objective tumor response among patients with measurable disease using modified RECIST1.1
  • Toxicity and tolerability of experimental arm [ Time Frame: 2 years ]
    Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Oral Calcitriol With Ketoconazole in CRPC
Official Title  ICMJE A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Calcitriol 10mcg QD X3, weekly + Ketoconazole 400mg po TID and Hydrocortisone 20mg AM, 10mg PM
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Castration-resistant Prostate Cancer
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Calcitriol, Ketoconazole, Hydrocortisone
Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).
Intervention: Drug: Calcitriol, Ketoconazole, Hydrocortisone
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 28, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: August 23, 2017)
Actual Study Completion Date  ICMJE February 28, 2018
Actual Primary Completion Date February 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

  11. Patients should be able to receive oral medications.
  12. Patients with brain metastases which are stable and have been treated with surgery and/or irradiation will be eligible for this trial.
  13. 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.
  14. Ability to understand and the willingness to sign a written informed consent document.
  15. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03261336
Other Study ID Numbers  ICMJE 16-2200
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Donald Trump, MD, Inova Health Care Services
Study Sponsor  ICMJE Donald Trump, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Skip (Donald) Trump, MD CEO & Executive Director Inova Schar Cancer Institute
PRS Account Inova Health Care Services
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP