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Castration-resistant Prostate CancerPhase 2NCT03261336

Oral Calcitriol With Ketoconazole in CRPC

A Phase 2 study testing Calcitriol, Ketoconazole, Hydrocortisone in people with Castration-resistant Prostate Cancer, run by Donald Trump, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Castration-resistant Prostate Cancer
What is being tested?
Calcitriol, Ketoconazole, Hydrocortisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
6 Jan 2017to 28 Feb 2018
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For inclusion in the trial, a patient must fulfill all of the following criteria:
  • 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.
  • Histologically or cytologically confirmed adenocarcinoma consistent clinically with androgen Independent prostate cancer
  • Measurable disease with elevated PSA or evaluable disease (PSA elevation will constitute evaluable disease).
  • 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.
  • 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.
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  • Patients must have prostate cancer that is advanced or recurrent.
  • Patients should not have received any chemotherapy or investigational agents for at least 28 days before entering the study.
  • Eastern Clinical Oncology Group performance status 0 or 1
  • Life expectancy >3 months.
  • 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
  • Patients should be able to receive oral medications.
  • Patients with brain metastases which are stable and have been treated with surgery and/or irradiation will be eligible for this trial.
  • 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.
  • Ability to understand and the willingness to sign a written informed consent document.
  • 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.

Who cannot join

  • Any of the following is a criterion for exclusion from the trial:
  • Known severe hypersensitivity to ketoconazole, calcitriol or any of the excipients of these products.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to calcitriol, ketoconazole, or other agents used in study.
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial.
  • History of kidney, ureteral, or bladder stones within the last 5 years
  • 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.
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  • Thiazide therapy within 7 days from entering the study.
  • Requirement for concurrent systemic glucocorticoid therapy at greater than physiologic replacement doses
  • Unwillingness to stop calcium supplementation.
  • 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.
  • 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.
  • 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
  • Concomitant use of proton pump inhibitors or H2 blockers
  • Treatment with a non-approved or investigational drug or agent within 28 days before day 1 of trial treatment.
  • Any unresolved chronic toxicity greater then CTC Grade 2 from previous anticancer therapy.
  • Incomplete healing from previous oncologic treatments or other major surgery.
  • Inability to swallow oral capsules.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

Other trials in United States

About this study

Official title: A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone

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

Read the 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

Being tested
Calcitriol, Ketoconazole, Hydrocortisone

What participants receive

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

  • Calcitriol, Ketoconazole, HydrocortisoneDrug

    Also called Rocaltrol®, active form of vitamin D3

    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

Study groups in NCT03261336
Study groupRoleWhat they receive
Calcitriol, Ketoconazole, HydrocortisoneExperimentalPatients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).
Receives: Drug: Calcitriol, Ketoconazole, Hydrocortisone

What is being measured

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

  1. PSA Response Rate

    Assessment of PSA every 4 weeks

    Measured: 2 years

Secondary outcomes (2)

  1. Tumor Response

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

    Measured: 2 years

  2. Toxicity and Tolerability of Experimental Arm

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

    Measured: 2 years

Timeline

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

  1. First posted25 Aug 2017
  2. Study start6 Jan 2017
  3. Primary completion28 Feb 2018
  4. Study completion28 Feb 2018

Why it stopped: can not meet enrollment

Resources

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
Not applicable
Intervention model
Single group
Model description
Calcitriol 10mcg QD X3, weekly + Ketoconazole 400mg po TID and Hydrocortisone 20mg AM, 10mg PM
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03261336
Sponsor's protocol ID
16-2200
Status last verified
Jan 2021
First submitted
12 Jul 2017
Last updated
8 Feb 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bikle DD, Pillai S. Vitamin D, calcium, and epidermal differentiation. Endocr Rev. 1993 Feb;14(1):3-19. doi: 10.1210/edrv-14-1-3. No abstract available.

    PubMed 8491153

  • McElwain MC, Dettlebach MA, Modzelewski RA, et al. Antiproliferative effects in vitro and in vivo of 1,25-dihydroxyvitamin D3 and a vitamin D3 analog in a squamous cell carcinoma model system Mol Cell Diff 3 (1) 31 (1995).

  • Modzelewski RA. Apoptotic effects of paclitaxel and calcitriol in rat dunning MLL and human PC-3 prostate tumor cells in vitro. Proc Amer Assoc Cancer Res 40 580, 1999.

  • Hershberger PA, Yu WD, Modzelewski RA, Rueger RM, Johnson CS, Trump DL. Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity in vitro and in vivo and accelerates paclitaxel-induced apoptosis. Clin Cancer Res. 2001 Apr;7(4):1043-51.

    PubMed 11309356

  • Light BW, Yu WD, McElwain MC, Russell DM, Trump DL, Johnson CS. Potentiation of cisplatin antitumor activity using a vitamin D analogue in a murine squamous cell carcinoma model system. Cancer Res. 1997 Sep 1;57(17):3759-64.

    PubMed 9288784

  • Hershberger PA, Modzelewski RA, Shurin ZR, Rueger RM, Trump DL, Johnson CS. 1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21(Waf1/Cip1) in vitro and in vivo. Cancer Res. 1999 Jun 1;59(11):2644-9.

    PubMed 10363987

  • McGuire TF, Trump DL, Johnson CS. Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1. J Biol Chem. 2001 Jul 13;276(28):26365-73. doi: 10.1074/jbc.M010101200. Epub 2001 Apr 30.

    PubMed 11331275

  • McGuire TF, Trump DL and Johnson CS. 1,25-dihydroxyvitamin D3 induces cytosolic accumulation of MEKK-1 before onset of apoptosis in a p38 MAPK-regulated manner. Proc. Amer. Assoc. Cancer Res. 2159, 435 (2002).

  • Hershberger PA, McGuire TF, Yu WD, Zuhowski EG, Schellens JH, Egorin MJ, Trump DL, Johnson CS. Cisplatin potentiates 1,25-dihydroxyvitamin D3-induced apoptosis in association with increased mitogen-activated protein kinase kinase kinase 1 (MEKK-1) expression. Mol Cancer Ther. 2002 Aug;1(10):821-9.

    PubMed 12492115

  • Johnson CS, Egorin MJ, Zuhowski R, 35 al. Effects of high dose calcitriol (1,25 dihydroxyvitamin D3) on the pharmacokinetics of paclitaxel or carboplatin: results of two phase I studies Amer Soc Clin Oncol 19 210a (2000).

  • Muindi JR, Peng Y, Potter DM, Hershberger PA, Tauch JS, Capozzoli MJ, Egorin MJ, Johnson CS, Trump DL. Pharmacokinetics of high-dose oral calcitriol: results from a phase 1 trial of calcitriol and paclitaxel. Clin Pharmacol Ther. 2002 Dec;72(6):648-59. doi: 10.1067/mcp.2002.129305.

    PubMed 12496746

  • Muindi JR, Modzelewski RA, Peng Y, Hershberger PA, Trump DL and Johnson CS. Plasma 1, 25-dihydroxycholecalciferol pharmacokinetics in normal and tumor bearing mice. Oncology (in press).

  • Yu WD, McElwain MC, Modzelewski RA, Russell DM, Smith DC, Trump DL, Johnson CS. Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone. J Natl Cancer Inst. 1998 Jan 21;90(2):134-41. doi: 10.1093/jnci/90.2.134.

    PubMed 9450573

  • Bernardi RJ, Trump DL, Yu WD, McGuire TF, Hershberger PA, Johnson CS. Combination of 1alpha,25-dihydroxyvitamin D(3) with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling. Clin Cancer Res. 2001 Dec;7(12):4164-73.

    PubMed 11751517

  • Klein RG, Arnaud SB, Gallagher JC, Deluca HF, Riggs BL. Intestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest. 1977 Jul;60(1):253-9. doi: 10.1172/JCI108762.

    PubMed 874087

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Calcitriol, Ketoconazole, Hydrocortisone in people with Castration-resistant Prostate Cancer, run by Donald Trump, MD 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 18 inclusion and 22 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: stopped early, as of the sponsor's last update on 8 Feb 2021. 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 8 Feb 2021). 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?

PSA Response Rate (time frame: 2 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 NCT03261336, which also lists 107 linked publications.

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 8 Feb 2021.

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