<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03261336</url>
  </required_header>
  <id_info>
    <org_study_id>16-2200</org_study_id>
    <nct_id>NCT03261336</nct_id>
  </id_info>
  <brief_title>Oral Calcitriol With Ketoconazole in CRPC</brief_title>
  <official_title>A Phase II Study of Oral Calcitriol in Combination With Ketoconazole in Castration Resistant Prostate Cancer, Progressing Despite Primary ADT and Abiraterone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Donald Trump, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Inova Health Care Services</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to estimate the PSA response rate with the use of ketoconazole&#xD;
      (400mg QD + hydrocortisone 20mg AM, 10 mg PM) among men with CRPC in whom disease has&#xD;
      progressed despite abiraterone&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will aim to describe objective tumor responses to the combination of oral&#xD;
      calcitriol and ketoconazole and hydrocortisone-among patients with measurable disease using&#xD;
      modified RECIST 1.1 criteria.&#xD;
&#xD;
      Additionally, we will determine toxicities, and tolerability of oral calcitriol combination&#xD;
      with daily oral ketoconazole, and hydrocortisone in this patient population.&#xD;
&#xD;
      this is a single arm phase II trial of ketoconazole (400mg QD + hydrocortisone 20mg AM, 10 mg&#xD;
      PM) among men with CRPC in whom disease has progressed despite abiraterone&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    can not meet enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">January 6, 2017</start_date>
  <completion_date type="Actual">February 28, 2018</completion_date>
  <primary_completion_date type="Actual">February 28, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Calcitriol 10mcg QD X3, weekly + Ketoconazole 400mg po TID and Hydrocortisone 20mg AM, 10mg PM</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PSA Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Assessment of PSA every 4 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor Response</measure>
    <time_frame>2 years</time_frame>
    <description>Objective tumor response among patients with measurable disease using modified RECIST1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity and Tolerability of Experimental Arm</measure>
    <time_frame>2 years</time_frame>
    <description>Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Castration-resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Calcitriol, Ketoconazole, Hydrocortisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitriol, Ketoconazole, Hydrocortisone</intervention_name>
    <description>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</description>
    <arm_group_label>Calcitriol, Ketoconazole, Hydrocortisone</arm_group_label>
    <other_name>Rocaltrol®</other_name>
    <other_name>active form of vitamin D3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        For inclusion in the trial, a patient must fulfill all of the following criteria:&#xD;
&#xD;
          1. Greater than or equal to 18 years of age. The effects of ketoconazole and high-dose&#xD;
             calcitriol have not been studied adequately in patients &lt;18 years of age and prostate&#xD;
             cancer has not been described in children.&#xD;
&#xD;
          2. Histologically or cytologically confirmed adenocarcinoma consistent clinically with&#xD;
             androgen Independent prostate cancer&#xD;
&#xD;
          3. Measurable disease with elevated PSA or evaluable disease (PSA elevation will&#xD;
             constitute evaluable disease).&#xD;
&#xD;
          4. No cytotoxic chemotherapy for extensive disease prior to study entry will be allowed;&#xD;
             given the recent data regarding the role of docetaxel + ADT in patients beginning ADT&#xD;
             for advanced disease, such &quot;adjuvant chemotherapy will be allowed (no more than 6&#xD;
             cycles) retinoids, vitamin D analogues, PPAR agonists or antagonists, antiandrogens,&#xD;
             progestational agents, estrogens, PC-SPES, LHRH analogues, vaccines, cytokines will&#xD;
             not be considered &quot;cytotoxics.&quot; Patients who have previously received ketoconazole +&#xD;
             glucocorticoids will NOT be eligible for this trial.&#xD;
&#xD;
          5. Patients who have received antiandrogens or progestational agents as therapy for&#xD;
             prostate cancer must discontinue therapy and demonstrate a rising PSA &gt; 28 days&#xD;
             following discontinuation (antiandrogen withdrawal - AAW) (&gt;42 days for bicalutamide&#xD;
             or nilutamide). Patients who receive megestrol acetate as therapy for &quot;hot flashes&quot; at&#xD;
             a dose of &lt;40mg per day may continue this therapy during this trial. The dose of the&#xD;
             megestrol acetate should not be changed during protocol treatment. Patients undergoing&#xD;
             androgen deprivation using LHRH analogues must continue such agents or undergo&#xD;
             orchiectomy to maintain castrate levels of testosterone.&#xD;
&#xD;
          6. Patients must have prostate cancer that is advanced or recurrent.&#xD;
&#xD;
          7. Patients should not have received any chemotherapy or investigational agents for at&#xD;
             least 28 days before entering the study.&#xD;
&#xD;
          8. Eastern Clinical Oncology Group performance status 0 or 1&#xD;
&#xD;
          9. Life expectancy &gt;3 months.&#xD;
&#xD;
         10. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
             leukocytes: &gt;3,000/μl hemoglobin: &gt; 8 g/dl absolute neutrophil count (ANC):&gt;1,500/μl&#xD;
             platelets: &gt;75,000/μl total bilirubin: within normal institutional limit AST/ALT: &lt;2.5&#xD;
             X institutional upper limit of normal creatinine: &lt; 2mg/dL calcium: not above normal&#xD;
             institutional limit&#xD;
&#xD;
         11. Patients should be able to receive oral medications.&#xD;
&#xD;
         12. Patients with brain metastases which are stable and have been treated with surgery&#xD;
             and/or irradiation will be eligible for this trial.&#xD;
&#xD;
         13. The effects of high-dose calcitriol and ketoconazole on the developing human fetus are&#xD;
             unknown. For this reason and because these agents as well are known to be teratogenic,&#xD;
             men must agree to use adequate contraception (hormonal or barrier method of birth&#xD;
             control; abstinence) prior to study entry and for the duration of study participation.&#xD;
             Should a woman become pregnant or suspect she is pregnant while her partner is&#xD;
             participating in this study, she should inform the treating physician immediately.&#xD;
&#xD;
         14. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
         15. Progressive disease must have occurred on abiraterone within the prior 12 months and&#xD;
             patient must not have received treatment with enzalutamide.&#xD;
&#xD;
        Men of all ethnic groups are eligible for this trial. Efforts will be made to include&#xD;
        minority groups and all representative ethnicities and races in the community.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Any of the following is a criterion for exclusion from the trial:&#xD;
&#xD;
          1. Known severe hypersensitivity to ketoconazole, calcitriol or any of the excipients of&#xD;
             these products.&#xD;
&#xD;
          2. History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to calcitriol, ketoconazole, or other agents used in study.&#xD;
&#xD;
          3. Evidence of any other significant clinical disorder or laboratory finding that makes&#xD;
             it undesirable for the patient to participate in the trial.&#xD;
&#xD;
          4. History of kidney, ureteral, or bladder stones within the last 5 years&#xD;
&#xD;
          5. Heart failure or significant heart disease including significant arrhythmias,&#xD;
             myocardial infarction within the last 3 months, unstable angina, documented ejection&#xD;
             fraction &lt;30%, or current digoxin therapy.&#xD;
&#xD;
          6. Thiazide therapy within 7 days from entering the study.&#xD;
&#xD;
          7. Requirement for concurrent systemic glucocorticoid therapy at greater than physiologic&#xD;
             replacement doses&#xD;
&#xD;
          8. Unwillingness to stop calcium supplementation.&#xD;
&#xD;
          9. As judged by the investigator, any evidence of severe or uncontrolled systemic disease&#xD;
             (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) or&#xD;
             intercurrent illness including, but not limited to, ongoing or active infection,&#xD;
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements.&#xD;
&#xD;
         10. Human immunodeficiency virus-positive patients receiving combination anti-retroviral&#xD;
             therapy are excluded from the study because of possible PK interactions with&#xD;
             ketoconazole or other agents administered during the study. Appropriate studies will&#xD;
             be undertaken in patients receiving combination anti-retroviral therapy when&#xD;
             indicated.&#xD;
&#xD;
         11. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital,&#xD;
             or St John's wort, alfentanil, alfuzosin, almotriptan, alprazolam, amiodarone,&#xD;
             amitriptyline, amprenavir, aprepitant, aripiprazole, bepridil, bortezomib, bosentan,&#xD;
             budesonide, buprenorphine, buspirone, carbamazepine, cilostazol, cisapride,&#xD;
             cyclosporine, delavirdine, didanosine, digoxin, disopyramidedofetilide, donepezil,&#xD;
             eletriptan, eplerenone, fluticasone, fosamprenavir, galantamine, systemic&#xD;
             griseofulvin, indinavir, levobupivacaine, lopinavir, midazolam, mifepristone,&#xD;
             modafinil, nateglinide, nefazadone, nelfinavir, oxcarbazepine, pimozide, quetiapine,&#xD;
             quinidine, repaglinide, rifabutin, rifampin, rifapentine, ritonavir, saquinavir,&#xD;
             sildenafil, sirolimus, tacrolimus, tadalafil, tolterodine, theophyllines, tolterodine,&#xD;
             triazolam, valdecoxib, vardenafil, ziprasidone, zonisamide, statins, with the&#xD;
             exception of pravastatin (Pravachol) or other &quot;statins&quot; which are not metabolized by&#xD;
             or induce CYP3A4, calcium channel blockers, and macrolides or other agents that will&#xD;
             be significantly perturbed in a clinically important way by the P450 inhibitory&#xD;
             properties of ketoconazole&#xD;
&#xD;
         12. Concomitant use of proton pump inhibitors or H2 blockers&#xD;
&#xD;
         13. Treatment with a non-approved or investigational drug or agent within 28 days before&#xD;
             day 1 of trial treatment.&#xD;
&#xD;
         14. Any unresolved chronic toxicity greater then CTC Grade 2 from previous anticancer&#xD;
             therapy.&#xD;
&#xD;
         15. Incomplete healing from previous oncologic treatments or other major surgery.&#xD;
&#xD;
         16. Inability to swallow oral capsules.&#xD;
&#xD;
         17. Patients on digoxin will be excluded from this study.&#xD;
&#xD;
        Products Dosage and Mode of Administration&#xD;
&#xD;
          -  Ketoconazole, 200 mg tablets, 2 tablets orally TID&#xD;
&#xD;
          -  Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days&#xD;
             every week&#xD;
&#xD;
          -  Hydrocortisone 20mg AM, 10mg PM orally starting in the evening before the first dose&#xD;
             of Calcitriol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Skip (Donald) Trump, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CEO &amp; Executive Director Inova Schar Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inova Schar Cancer Institute</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>8491153</PMID>
  </reference>
  <reference>
    <citation>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).</citation>
  </reference>
  <reference>
    <citation>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.</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11309356</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>9288784</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>10363987</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11331275</PMID>
  </reference>
  <reference>
    <citation>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).</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>12492115</PMID>
  </reference>
  <reference>
    <citation>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).</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>12496746</PMID>
  </reference>
  <reference>
    <citation>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).</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>9450573</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11751517</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>874087</PMID>
  </reference>
  <reference>
    <citation>Ahmed S, Johnson CS, Rueger RM, Trump DL. Calcitriol (1,25-dihydroxycholecalciferol) potentiates activity of mitoxantrone/dexamethasone in an androgen independent prostate cancer model. J Urol. 2002 Aug;168(2):756-61.</citation>
    <PMID>12131364</PMID>
  </reference>
  <reference>
    <citation>Hershberger PA, Modzelewski RA, Rueger RM, Blum KE, Trump DL, and Johnson CS. Enhanced anti-tumor efficacy with dexamethasone/calcitriol/cisplatin therapy: role of P21WAF1. Proc. Amer. Assoc. Cancer Res. 41, 15 (2000).</citation>
  </reference>
  <reference>
    <citation>Yu WD, Rueger RM, Fuller RW, Johnson CS, and Trump DL. 1,25-dihydroxycholecalciferol (calcitriol) enhancement of chemotherapeutic efficacy: synergistic effects by median dose effect. Proc. Amer. Assoc. Cancer Res. 42, 84 (2001).</citation>
  </reference>
  <reference>
    <citation>Trump DL, Serafine S, Brufsky J, et al. High dose calcitriol (1,25(OH)2 vitamin D3) + dexamethasone in androgen independent prostate cancer (AIPC). Amer Soc Clin Oncol 19 337a (2000).</citation>
  </reference>
  <reference>
    <citation>Omdahl JL, Bobrovnikova EA, Choe S, Dwivedi PP, May BK. Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway. Steroids. 2001 Mar-May;66(3-5):381-9. doi: 10.1016/s0039-128x(00)00157-4.</citation>
    <PMID>11179747</PMID>
  </reference>
  <reference>
    <citation>Feldman D. Ketoconazole and other imidazole derivatives as inhibitors of steroidogenesis. Endocr Rev. 1986 Nov;7(4):409-20. doi: 10.1210/edrv-7-4-409. No abstract available.</citation>
    <PMID>3536461</PMID>
  </reference>
  <reference>
    <citation>Reinhardt TA, Horst RL. Ketoconazole inhibits self-induced metabolism of 1,25-dihydroxyvitamin D3 and amplifies 1,25-dihydroxyvitamin D3 receptor up-regulation in rat osteosarcoma cells. Arch Biochem Biophys. 1989 Aug 1;272(2):459-65. doi: 10.1016/0003-9861(89)90240-3.</citation>
    <PMID>2546501</PMID>
  </reference>
  <reference>
    <citation>Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889-95. doi: 10.1126/science.3283939.</citation>
    <PMID>3283939</PMID>
  </reference>
  <reference>
    <citation>Darwish HM, DeLuca HF. Recent advances in the molecular biology of vitamin D action. Prog Nucleic Acid Res Mol Biol. 1996;53:321-44. doi: 10.1016/s0079-6603(08)60149-x.</citation>
    <PMID>8650307</PMID>
  </reference>
  <reference>
    <citation>Christakos S, Raval-Pandya M, Wernyj RP, Yang W. Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3. Biochem J. 1996 Jun 1;316 ( Pt 2)(Pt 2):361-71. doi: 10.1042/bj3160361. Erratum In: Biochem J 1996 Sep 15;318(Pt 3):1079.</citation>
    <PMID>8687373</PMID>
  </reference>
  <reference>
    <citation>Darwish H, DeLuca HF. Vitamin D-regulated gene expression. Crit Rev Eukaryot Gene Expr. 1993;3(2):89-116.</citation>
    <PMID>8391882</PMID>
  </reference>
  <reference>
    <citation>Studzinski GP, McLane JA, Uskokovic MR. Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases. Crit Rev Eukaryot Gene Expr. 1993;3(4):279-312.</citation>
    <PMID>8286848</PMID>
  </reference>
  <reference>
    <citation>Weigel NL. Steroid hormone receptors and their regulation by phosphorylation. Biochem J. 1996 Nov 1;319 ( Pt 3)(Pt 3):657-67. doi: 10.1042/bj3190657.</citation>
    <PMID>8920964</PMID>
  </reference>
  <reference>
    <citation>Norman AW, Nemere I, Zhou LX, Bishop JE, Lowe KE, Maiyar AC, Collins ED, Taoka T, Sergeev I, Farach-Carson MC. 1,25(OH)2-vitamin D3, a steroid hormone that produces biologic effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):231-40. doi: 10.1016/0960-0760(92)90349-n.</citation>
    <PMID>1314073</PMID>
  </reference>
  <reference>
    <citation>Slater SJ, Kelly MB, Taddeo FJ, Larkin JD, Yeager MD, McLane JA, Ho C, Stubbs CD. Direct activation of protein kinase C by 1 alpha,25-dihydroxyvitamin D3. J Biol Chem. 1995 Mar 24;270(12):6639-43. doi: 10.1074/jbc.270.12.6639.</citation>
    <PMID>7896803</PMID>
  </reference>
  <reference>
    <citation>de Boland AR, Morelli S, Boland R. 1,25(OH)2-vitamin D3 signal transduction in chick myoblasts involves phosphatidylcholine hydrolysis. J Biol Chem. 1994 Mar 25;269(12):8675-9.</citation>
    <PMID>8132595</PMID>
  </reference>
  <reference>
    <citation>Khare S, Tien XY, Wilson D, Wali RK, Bissonnette BM, Scaglione-Sewell B, Sitrin MD, Brasitus TA. The role of protein kinase-C alpha in the activation of particulate guanylate cyclase by 1 alpha,25-dihydroxyvitamin D3 in CaCo-2 cells. Endocrinology. 1994 Jul;135(1):277-83. doi: 10.1210/endo.135.1.7912183.</citation>
    <PMID>7912183</PMID>
  </reference>
  <reference>
    <citation>de Boland AR, Norman A. Evidence for involvement of protein kinase C and cyclic adenosine 3',5' monophosphate-dependent protein kinase in the 1,25-dihydroxy-vitamin D3-mediated rapid stimulation of intestinal calcium transport, (transcaltachia). Endocrinology. 1990 Jul;127(1):39-45. doi: 10.1210/endo-127-1-39.</citation>
    <PMID>2163320</PMID>
  </reference>
  <reference>
    <citation>Gniadecki R. Activation of Raf-mitogen-activated protein kinase signaling pathway by 1,25-dihydroxyvitamin D3 in normal human keratinocytes. J Invest Dermatol. 1996 Jun;106(6):1212-7. doi: 10.1111/1523-1747.ep12348498.</citation>
    <PMID>8752659</PMID>
  </reference>
  <reference>
    <citation>MacDonald PN, Baudino TA, Tokumaru H, Dowd DR, Zhang C. Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription. Steroids. 2001 Mar-May;66(3-5):171-6. doi: 10.1016/s0039-128x(00)00200-2.</citation>
    <PMID>11179724</PMID>
  </reference>
  <reference>
    <citation>Barletta F, Freedman LP, Christakos S. Enhancement of VDR-mediated transcription by phosphorylation: correlation with increased interaction between the VDR and DRIP205, a subunit of the VDR-interacting protein coactivator complex. Mol Endocrinol. 2002 Feb;16(2):301-14. doi: 10.1210/mend.16.2.0764.</citation>
    <PMID>11818502</PMID>
  </reference>
  <reference>
    <citation>Zhang C, Dowd DR, Staal A, Gu C, Lian JB, van Wijnen AJ, Stein GS, MacDonald PN. Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. J Biol Chem. 2003 Sep 12;278(37):35325-36. doi: 10.1074/jbc.M305191200. Epub 2003 Jul 2.</citation>
    <PMID>12840015</PMID>
  </reference>
  <reference>
    <citation>Herdick M, Carlberg C. Agonist-triggered modulation of the activated and silent state of the vitamin D(3) receptor by interaction with co-repressors and co-activators. J Mol Biol. 2000 Dec 15;304(5):793-801. doi: 10.1006/jmbi.2000.4267.</citation>
    <PMID>11124027</PMID>
  </reference>
  <reference>
    <citation>Colston KW, Chander SK, Mackay AG, Coombes RC. Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol. 1992 Aug 18;44(4):693-702. doi: 10.1016/0006-2952(92)90405-8.</citation>
    <PMID>1324683</PMID>
  </reference>
  <reference>
    <citation>Frappart L, Falette N, Lefebvre MF, Bremond A, Vauzelle JL, Saez S. In vitro study of effects of 1,25 dihydroxyvitamin D3 on the morphology of human breast cancer cell line BT.20. Differentiation. 1989 Mar;40(1):63-9. doi: 10.1111/j.1432-0436.1989.tb00814.x.</citation>
    <PMID>2545494</PMID>
  </reference>
  <reference>
    <citation>Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SR. 1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Res. 1993 Aug 15;53(16):3712-8.</citation>
    <PMID>8393379</PMID>
  </reference>
  <reference>
    <citation>Mangelsdorf DJ, Koeffler HP, Donaldson CA, Pike JW, Haussler MR. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J Cell Biol. 1984 Feb;98(2):391-8. doi: 10.1083/jcb.98.2.391.</citation>
    <PMID>6319426</PMID>
  </reference>
  <reference>
    <citation>Godyn JJ, Xu H, Zhang F, Kolla S, Studzinski GP. A dual block to cell cycle progression in HL60 cells exposed to analogues of vitamin D3. Cell Prolif. 1994 Jan;27(1):37-46. doi: 10.1111/j.1365-2184.1994.tb01404.x.</citation>
    <PMID>10465025</PMID>
  </reference>
  <reference>
    <citation>Rigby WF, Noelle RJ, Krause K, Fanger MW. The effects of 1,25-dihydroxyvitamin D3 on human T lymphocyte activation and proliferation: a cell cycle analysis. J Immunol. 1985 Oct;135(4):2279-86.</citation>
    <PMID>2993410</PMID>
  </reference>
  <reference>
    <citation>Wang QM, Jones JB, Studzinski GP. Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. Cancer Res. 1996 Jan 15;56(2):264-7.</citation>
    <PMID>8542578</PMID>
  </reference>
  <reference>
    <citation>Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996 Jan 15;10(2):142-53. doi: 10.1101/gad.10.2.142.</citation>
    <PMID>8566748</PMID>
  </reference>
  <reference>
    <citation>Biggs JR, Kraft AS. Inhibitors of cyclin-dependent kinase and cancer. J Mol Med (Berl). 1995 Oct;73(10):509-14. doi: 10.1007/BF00198902.</citation>
    <PMID>8581512</PMID>
  </reference>
  <reference>
    <citation>Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995 May 15;9(10):1149-63. doi: 10.1101/gad.9.10.1149. No abstract available.</citation>
    <PMID>7758941</PMID>
  </reference>
  <reference>
    <citation>Sheikh MS, Rochefort H, Garcia M. Overexpression of p21WAF1/CIP1 induces growth arrest, giant cell formation and apoptosis in human breast carcinoma cell lines. Oncogene. 1995 Nov 2;11(9):1899-905.</citation>
    <PMID>7478620</PMID>
  </reference>
  <reference>
    <citation>Henkart PA. ICE family proteases: mediators of all apoptotic cell death? Immunity. 1996 Mar;4(3):195-201. doi: 10.1016/s1074-7613(00)80428-8. No abstract available.</citation>
    <PMID>8624810</PMID>
  </reference>
  <reference>
    <citation>Hockenbery DM. The bcl-2 oncogene and apoptosis. Semin Immunol. 1992 Dec;4(6):413-20.</citation>
    <PMID>1286168</PMID>
  </reference>
  <reference>
    <citation>Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh J. 1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 1996 Jul;58(4):367-76. doi: 10.1016/0960-0760(96)00055-6.</citation>
    <PMID>8903420</PMID>
  </reference>
  <reference>
    <citation>Xu HM, Tepper CG, Jones JB, Fernandez CE, Studzinski GP. 1,25-Dihydroxyvitamin D3 protects HL60 cells against apoptosis but down-regulates the expression of the bcl-2 gene. Exp Cell Res. 1993 Dec;209(2):367-74. doi: 10.1006/excr.1993.1322.</citation>
    <PMID>8262155</PMID>
  </reference>
  <reference>
    <citation>Henry HL. The 25(OH)D(3)/1alpha,25(OH)(2)D(3)-24R-hydroxylase: a catabolic or biosynthetic enzyme? Steroids. 2001 Mar-May;66(3-5):391-8. doi: 10.1016/s0039-128x(00)00158-6.</citation>
    <PMID>11179748</PMID>
  </reference>
  <reference>
    <citation>Miller GJ, Stapleton GE, Hedlund TE, Moffat KA. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res. 1995 Sep;1(9):997-1003.</citation>
    <PMID>9816072</PMID>
  </reference>
  <reference>
    <citation>Bareis P, Bises G, Bischof MG, Cross HS, Peterlik M. 25-hydroxy-vitamin d metabolism in human colon cancer cells during tumor progression. Biochem Biophys Res Commun. 2001 Jul 27;285(4):1012-7. doi: 10.1006/bbrc.2001.5289.</citation>
    <PMID>11467853</PMID>
  </reference>
  <reference>
    <citation>Zhao J, Tan BK, Marcelis S, Verstuyf A, Bouillon R. Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific. J Steroid Biochem Mol Biol. 1996 Feb;57(3-4):197-202. doi: 10.1016/0960-0760(95)00256-1.</citation>
    <PMID>8645629</PMID>
  </reference>
  <reference>
    <citation>Peehl DM, Seto E, Hsu JY, Feldman D. Preclinical activity of ketoconazole in combination with calcitriol or the vitamin D analogue EB 1089 in prostate cancer cells. J Urol. 2002 Oct;168(4 Pt 1):1583-8. doi: 10.1097/01.ju.0000030158.18335.84.</citation>
    <PMID>12352462</PMID>
  </reference>
  <reference>
    <citation>Ly LH, Zhao XY, Holloway L, Feldman D. Liarozole acts synergistically with 1alpha,25-dihydroxyvitamin D3 to inhibit growth of DU 145 human prostate cancer cells by blocking 24-hydroxylase activity. Endocrinology. 1999 May;140(5):2071-6. doi: 10.1210/endo.140.5.6698.</citation>
    <PMID>10218956</PMID>
  </reference>
  <reference>
    <citation>Strom M, Sandgren ME, Brown TA, DeLuca HF. 1,25-Dihydroxyvitamin D3 up-regulates the 1,25-dihydroxyvitamin D3 receptor in vivo. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9770-3. doi: 10.1073/pnas.86.24.9770.</citation>
    <PMID>2481316</PMID>
  </reference>
  <reference>
    <citation>Chen TL, Cone CM, Morey-Holton E, Feldman D. Glucocorticoid regulation of 1,25(OH)2-vitamin D3 receptors in cultured mouse bone cells. J Biol Chem. 1982 Nov 25;257(22):13564-9. No abstract available.</citation>
    <PMID>6292196</PMID>
  </reference>
  <reference>
    <citation>Levy J, Zuili I, Yankowitz N, Shany S. Induction of cytosolic receptors for 1 alpha, 25-dihydroxyvitamin D3 in the immature rat uterus by oestradiol. J Endocrinol. 1984 Mar;100(3):265-9. doi: 10.1677/joe.0.1000265.</citation>
    <PMID>6321624</PMID>
  </reference>
  <reference>
    <citation>Petkovich PM, Heersche JN, Tinker DO, Jones G. Retinoic acid stimulates 1,25-dihydroxyvitamin D3 binding in rat osteosarcoma cells. J Biol Chem. 1984 Jul 10;259(13):8274-80.</citation>
    <PMID>6330107</PMID>
  </reference>
  <reference>
    <citation>Reinhardt TA, Horst RL. Parathyroid hormone down-regulates 1,25-dihydroxyvitamin D receptors (VDR) and VDR messenger ribonucleic acid in vitro and blocks homologous up-regulation of VDR in vivo. Endocrinology. 1990 Aug;127(2):942-8. doi: 10.1210/endo-127-2-942.</citation>
    <PMID>2164926</PMID>
  </reference>
  <reference>
    <citation>Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 1995 Apr;16(2):200-57. doi: 10.1210/edrv-16-2-200. No abstract available.</citation>
    <PMID>7781594</PMID>
  </reference>
  <reference>
    <citation>Trump DL, Havlin KH, Messing EM, Cummings KB, Lange PH, Jordan VC. High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. J Clin Oncol. 1989 Aug;7(8):1093-8. doi: 10.1200/JCO.1989.7.8.1093.</citation>
    <PMID>2474059</PMID>
  </reference>
  <reference>
    <citation>OH WK. Secondary hormonal therapies in the treatment of prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):87-92; discussion 93. doi: 10.1016/s0090-4295(02)01581-9.</citation>
    <PMID>12231058</PMID>
  </reference>
  <reference>
    <citation>Hirst M, Feldman D. Glucocorticoids down-regulate the number of 1, 25-dihydroxyvitamin D3 receptors in mouse intestine. Biochem Biophys Res Commun. 1982 Apr 29;105(4):1590-6. doi: 10.1016/0006-291x(82)90970-6. No abstract available.</citation>
    <PMID>6285911</PMID>
  </reference>
  <reference>
    <citation>Kimberg DV, Baerg RD, Gershon E, Graudusius RT. Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest. 1971 Jun;50(6):1309-21. doi: 10.1172/JCI106610.</citation>
    <PMID>4325312</PMID>
  </reference>
  <reference>
    <citation>Haynes RC. Agents affecting calcification: calcium, parathyroid hormone, calcitonin, vitamin D, and other compounds. The Pharmacological Basis of Therapeutics. Gilman AG, Rall TW, Nies AS, Taylor P (eds). New York Pergamon Press 1496 (1990).</citation>
  </reference>
  <reference>
    <citation>Fakih M, Johnson CS, Trump DL. Glucocorticoids and treatment of prostate cancer: a preclinical and clinical review. Urology. 2002 Oct;60(4):553-61. doi: 10.1016/s0090-4295(02)01741-7. No abstract available.</citation>
    <PMID>12385906</PMID>
  </reference>
  <reference>
    <citation>Nishimura K, Nonomura N, Satoh E, Harada Y, Nakayama M, Tokizane T, Fukui T, Ono Y, Inoue H, Shin M, Tsujimoto Y, Takayama H, Aozasa K, Okuyama A. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst. 2001 Nov 21;93(22):1739-46. doi: 10.1093/jnci/93.22.1739.</citation>
    <PMID>11717335</PMID>
  </reference>
  <reference>
    <citation>Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. doi: 10.1200/JCO.1996.14.6.1756.</citation>
    <PMID>8656243</PMID>
  </reference>
  <reference>
    <citation>Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. doi: 10.1200/JCO.1999.17.8.2506.</citation>
    <PMID>10561316</PMID>
  </reference>
  <reference>
    <citation>Small EJ, Meyer M, Marshall ME, Reyno LM, Meyers FJ, Natale RB, Lenehan PF, Chen L, Slichenmyer WJ, Eisenberger M. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol. 2000 Apr;18(7):1440-50. doi: 10.1200/JCO.2000.18.7.1440.</citation>
    <PMID>10735891</PMID>
  </reference>
  <reference>
    <citation>Cunningham D, Gilchrist NL, Cowan RA, Forrest GJ, McArdle CS, Soukop M. Alfacalcidol as a modulator of growth of low grade non-Hodgkin's lymphomas. Br Med J (Clin Res Ed). 1985 Oct 26;291(6503):1153-5. doi: 10.1136/bmj.291.6503.1153.</citation>
    <PMID>2996693</PMID>
  </reference>
  <reference>
    <citation>Koeffler HP, Hirji K, Itri L. 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treat Rep. 1985 Dec;69(12):1399-407.</citation>
    <PMID>2416438</PMID>
  </reference>
  <reference>
    <citation>Rolla D, Paoletti E, Marsano L, Mulas D, Peloso G, Cannella G. Effects of subcutaneous calcitriol administration on plasma calcium and parathyroid hormone concentrations in continuous ambulatory peritoneal dialysis uremic patients. Perit Dial Int. 1993;13(2):118-21.</citation>
    <PMID>8494932</PMID>
  </reference>
  <reference>
    <citation>Davies M. High-dose vitamin D therapy: indications, benefits and hazards. Int J Vitam Nutr Res Suppl. 1989;30:81-6.</citation>
    <PMID>2507709</PMID>
  </reference>
  <reference>
    <citation>Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW, Trump DL. A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res. 1999 Jun;5(6):1339-45.</citation>
    <PMID>10389917</PMID>
  </reference>
  <reference>
    <citation>Beer TM, Munar M, Henner WD. A Phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation. Cancer. 2001 Jun 15;91(12):2431-9.</citation>
    <PMID>11413535</PMID>
  </reference>
  <reference>
    <citation>Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol. 2003 Jan 1;21(1):123-8. doi: 10.1200/jco.2003.05.117.</citation>
    <PMID>12506180</PMID>
  </reference>
  <reference>
    <citation>Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 1993 Sep 1;53(17):3976-85.</citation>
    <PMID>8358726</PMID>
  </reference>
  <reference>
    <citation>Paul A, Wilson S, Belham CM, Robinson CJ, Scott PH, Gould GW, Plevin R. Stress-activated protein kinases: activation, regulation and function. Cell Signal. 1997 Sep;9(6):403-10. doi: 10.1016/s0898-6568(97)00042-9.</citation>
    <PMID>9376221</PMID>
  </reference>
  <reference>
    <citation>Lewis TS, Shapiro PS, Ahn NG. Signal transduction through MAP kinase cascades. Adv Cancer Res. 1998;74:49-139. doi: 10.1016/s0065-230x(08)60765-4. No abstract available.</citation>
    <PMID>9561267</PMID>
  </reference>
  <reference>
    <citation>Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G. The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci. 2000 May;113 ( Pt 10):1661-70. doi: 10.1242/jcs.113.10.1661.</citation>
    <PMID>10769197</PMID>
  </reference>
  <reference>
    <citation>Yu WD, Chang MJ, Trump DL, Johnson CS. Interleukin-1alpha synergistic in vivo enhancement of cyclophosphamide- and carboplatin-mediated antitumor activity. Cancer Immunol Immunother. 1997 Aug;44(6):316-22. doi: 10.1007/s002620050388.</citation>
    <PMID>9298933</PMID>
  </reference>
  <reference>
    <citation>Kim D, Gregory CW, French FS, Smith GJ, Mohler JL. Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft. Am J Pathol. 2002 Jan;160(1):219-26. doi: 10.1016/S0002-9440(10)64365-9.</citation>
    <PMID>11786415</PMID>
  </reference>
  <reference>
    <citation>Gregory CW, Kim D, Ye P, D'Ercole AJ, Pretlow TG, Mohler JL, French FS. Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology. 1999 May;140(5):2372-81. doi: 10.1210/endo.140.5.6702.</citation>
    <PMID>10218991</PMID>
  </reference>
  <reference>
    <citation>Smitherman AB, Mohler JL, Maygarden SJ, Ornstein DK. Expression of annexin I, II and VII proteins in androgen stimulated and recurrent prostate cancer. J Urol. 2004 Feb;171(2 Pt 1):916-20. doi: 10.1097/01.ju.0000104674.70170.cd.</citation>
    <PMID>14713853</PMID>
  </reference>
  <reference>
    <citation>Smitherman AB, Gregory CW, Mohler JL. Apoptosis levels increase after castration in the CWR22 human prostate cancer xenograft. Prostate. 2003 Sep 15;57(1):24-31. doi: 10.1002/pros.10271.</citation>
    <PMID>12886520</PMID>
  </reference>
  <reference>
    <citation>Mohler JL, Morris TL, Ford OH 3rd, Alvey RF, Sakamoto C, Gregory CW. Identification of differentially expressed genes associated with androgen-independent growth of prostate cancer. Prostate. 2002 Jun 1;51(4):247-55. doi: 10.1002/pros.10086.</citation>
    <PMID>11987153</PMID>
  </reference>
  <reference>
    <citation>Kurahashi I, Matsunuma A, Kawane T, Abe M, Horiuchi N. Dexamethasone enhances vitamin D-24-hydroxylase expression in osteoblastic (UMR-106) and renal (LLC-PK1) cells treated with 1alpha,25-dihydroxyvitamin D3. Endocrine. 2002 Mar;17(2):109-18. doi: 10.1385/ENDO:17:2:109.</citation>
    <PMID>12041912</PMID>
  </reference>
  <reference>
    <citation>Akeno N, Matsunuma A, Maeda T, Kawane T, Horiuchi N. Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney. J Endocrinol. 2000 Mar;164(3):339-48. doi: 10.1677/joe.0.1640339.</citation>
    <PMID>10694374</PMID>
  </reference>
  <reference>
    <citation>Kang S, Li XY, Duell EA, Voorhees JJ. The retinoid X receptor agonist 9-cis-retinoic acid and the 24-hydroxylase inhibitor ketoconazole increase activity of 1,25-dihydroxyvitamin D3 in human skin in vivo. J Invest Dermatol. 1997 Apr;108(4):513-8. doi: 10.1111/1523-1747.ep12289736.</citation>
    <PMID>9077483</PMID>
  </reference>
  <reference>
    <citation>Schuster I, Egger H, Bikle D, Herzig G, Reddy GS, Stuetz A, Stuetz P, Vorisek G. Selective inhibition of vitamin D hydroxylases in human keratinocytes. Steroids. 2001 Mar-May;66(3-5):409-22. doi: 10.1016/s0039-128x(00)00159-8.</citation>
    <PMID>11179750</PMID>
  </reference>
  <reference>
    <citation>Sakaki T, Sawada N, Abe D, Komai K, Shiozawa S, Nonaka Y, Nakagawa K, Okano T, Ohta M, Inouye K. Metabolism of 26,26,26,27,27,27-F6-1alpha,25-dihydroxyvitamin D3 by CYP24: species-based difference between humans and rats. Biochem Pharmacol. 2003 Jun 15;65(12):1957-65. doi: 10.1016/s0006-2952(03)00190-4.</citation>
    <PMID>12787875</PMID>
  </reference>
  <reference>
    <citation>Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods. 2002 Feb;26(2):199-213. doi: 10.1016/S1046-2023(02)00023-3.</citation>
    <PMID>12054897</PMID>
  </reference>
  <reference>
    <citation>Kuo MH, Allis CD. In vivo cross-linking and immunoprecipitation for studying dynamic Protein:DNA associations in a chromatin environment. Methods. 1999 Nov;19(3):425-33. doi: 10.1006/meth.1999.0879.</citation>
    <PMID>10579938</PMID>
  </reference>
  <reference>
    <citation>Smith ML. Mdm2 sensitizes MCF7 breast cancer cells to cisplatin or carboplatin. Breast Cancer Res Treat. 1999 Nov;58(2):99-105. doi: 10.1023/a:1006390107197.</citation>
    <PMID>10674873</PMID>
  </reference>
  <reference>
    <citation>Fillippovich I, Sorokina N, Gatei M, Haupt Y, Hobson K, Moallem E, Spring K, Mould M, McGuckin MA, Lavin MF, Khanna KK. Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53. Oncogene. 2001 Jan 25;20(4):514-22. doi: 10.1038/sj.onc.1204118.</citation>
    <PMID>11313982</PMID>
  </reference>
  <reference>
    <citation>Mandic A, Viktorsson K, Molin M, Akusjarvi G, Eguchi H, Hayashi SI, Toi M, Hansson J, Linder S, Shoshan MC. Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner. Mol Cell Biol. 2001 Jun;21(11):3684-91. doi: 10.1128/MCB.21.11.3684-3691.2001.</citation>
    <PMID>11340162</PMID>
  </reference>
  <reference>
    <citation>Mabuchi S, Ohmichi M, Kimura A, Hisamoto K, Hayakawa J, Nishio Y, Adachi K, Takahashi K, Arimoto-Ishida E, Nakatsuji Y, Tasaka K, Murata Y. Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel. J Biol Chem. 2002 Sep 6;277(36):33490-500. doi: 10.1074/jbc.M204042200. Epub 2002 Jun 26.</citation>
    <PMID>12087097</PMID>
  </reference>
  <reference>
    <citation>Hisamoto K, Ohmichi M, Kanda Y, Adachi K, Nishio Y, Hayakawa J, Mabuchi S, Takahashi K, Tasaka K, Miyamoto Y, Taniguchi N, Murata Y. Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene analog LY117018 is differentially mediated by Akt and extracellular signal-regulated protein kinase in vascular endothelial cells. J Biol Chem. 2001 Dec 14;276(50):47642-9. doi: 10.1074/jbc.M103853200. Epub 2001 Oct 10.</citation>
    <PMID>11595733</PMID>
  </reference>
  <reference>
    <citation>Dent P, Grant S. Pharmacologic interruption of the mitogen-activated extracellular-regulated kinase/mitogen-activated protein kinase signal transduction pathway: potential role in promoting cytotoxic drug action. Clin Cancer Res. 2001 Apr;7(4):775-83. No abstract available.</citation>
    <PMID>11309321</PMID>
  </reference>
  <reference>
    <citation>Agoulnik IU, Krause WC, Bingman WE 3rd, Rahman HT, Amrikachi M, Ayala GE, Weigel NL. Repressors of androgen and progesterone receptor action. J Biol Chem. 2003 Aug 15;278(33):31136-48. doi: 10.1074/jbc.M305153200. Epub 2003 May 27.</citation>
    <PMID>12771131</PMID>
  </reference>
  <reference>
    <citation>Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129-56. doi: 10.1146/annurev.med.48.1.129.</citation>
    <PMID>9046951</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <results_first_submitted>January 19, 2021</results_first_submitted>
  <results_first_submitted_qc>January 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 8, 2021</results_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Inova Health Care Services</investigator_affiliation>
    <investigator_full_name>Donald Trump, MD</investigator_full_name>
    <investigator_title>CEO &amp; Executive Director, Inova Schar Cancer Institute</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Calcitriol</mesh_term>
    <mesh_term>Ketoconazole</mesh_term>
    <mesh_term>Hydrocortisone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT03261336/ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT03261336/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_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.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
          <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
          <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78" lower_limit="78" upper_limit="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>PSA Response Rate</title>
        <description>Assessment of PSA every 4 weeks</description>
        <time_frame>2 years</time_frame>
        <population>Only one patient enrolled to study and was discontinued early due to AE.</population>
        <group_list>
          <group group_id="O1">
            <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
            <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
          </group>
        </group_list>
        <measure>
          <title>PSA Response Rate</title>
          <description>Assessment of PSA every 4 weeks</description>
          <population>Only one patient enrolled to study and was discontinued early due to AE.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Response</title>
        <description>Objective tumor response among patients with measurable disease using modified RECIST1.1</description>
        <time_frame>2 years</time_frame>
        <population>Only one patient was enrolled and was discontinued due to AE.</population>
        <group_list>
          <group group_id="O1">
            <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
            <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Response</title>
          <description>Objective tumor response among patients with measurable disease using modified RECIST1.1</description>
          <population>Only one patient was enrolled and was discontinued due to AE.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity and Tolerability of Experimental Arm</title>
        <description>Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment</description>
        <time_frame>2 years</time_frame>
        <population>Patient developed hypercalcemia and was discontinued from study. AE is known, not unexpected.</population>
        <group_list>
          <group group_id="O1">
            <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
            <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity and Tolerability of Experimental Arm</title>
          <description>Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment</description>
          <population>Patient developed hypercalcemia and was discontinued from study. AE is known, not unexpected.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AE data was collected on a single patient during one month in 2017.</time_frame>
      <desc>Definition consistent with clinicaltrials.gov</desc>
      <group_list>
        <group group_id="E1">
          <title>Calcitriol, Ketoconazole, Hydrocortisone</title>
          <description>Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).&#xD;
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</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>hypercalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_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.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Stephanie Van Bebber, Sr. Director Clinical Trials</name_or_title>
      <organization>Inova Schar Cancer Institute</organization>
      <phone>5714720213</phone>
      <email>Stephanie.VanBebber@inova.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03261336
org study id: 16-2200
nct id: NCT03261336
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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
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
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 PM
primary purpose: Treatment
masking: None (Open Label)
measure: PSA Response Rate
time frame: 2 years
description: Assessment of PSA every 4 weeks
measure: Tumor Response
time frame: 2 years
description: Objective tumor response among patients with measurable disease using modified RECIST1.1
measure: Toxicity and Tolerability of Experimental Arm
time frame: 2 years
description: Descriptive analysis of observed toxicity and patient reports of tolerating experimental treatment
arm group label: Calcitriol, Ketoconazole, Hydrocortisone
arm group type: Experimental
description: Patients receive calcitriol (10mcg QD X3 weekly) in addition to ketoconazole (400mg QD) and hydrocortisone (20mg AM, 10 mg PM).
intervention type: Drug
intervention name: Calcitriol, Ketoconazole, Hydrocortisone
description: 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
arm group label: Calcitriol, Ketoconazole, Hydrocortisone
other name: Rocaltrol®
other name: active form of vitamin D3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Skip (Donald) Trump, MD
role: Principal Investigator
affiliation: CEO & Executive Director Inova Schar Cancer Institute
facility: 
country: United States
citation: 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.
PMID: 8491153
citation: 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).
citation: 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.
citation: 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.
PMID: 11309356
citation: 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.
PMID: 9288784
citation: 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.
PMID: 10363987
citation: 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.
PMID: 11331275
citation: 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).
citation: 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.
PMID: 12492115
citation: 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).
citation: 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.
PMID: 12496746
citation: 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).
citation: 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.
PMID: 9450573
citation: 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.
PMID: 11751517
citation: 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.
PMID: 874087
citation: Ahmed S, Johnson CS, Rueger RM, Trump DL. Calcitriol (1,25-dihydroxycholecalciferol) potentiates activity of mitoxantrone/dexamethasone in an androgen independent prostate cancer model. J Urol. 2002 Aug;168(2):756-61.
PMID: 12131364
citation: Hershberger PA, Modzelewski RA, Rueger RM, Blum KE, Trump DL, and Johnson CS. Enhanced anti-tumor efficacy with dexamethasone/calcitriol/cisplatin therapy: role of P21WAF1. Proc. Amer. Assoc. Cancer Res. 41, 15 (2000).
citation: Yu WD, Rueger RM, Fuller RW, Johnson CS, and Trump DL. 1,25-dihydroxycholecalciferol (calcitriol) enhancement of chemotherapeutic efficacy: synergistic effects by median dose effect. Proc. Amer. Assoc. Cancer Res. 42, 84 (2001).
citation: Trump DL, Serafine S, Brufsky J, et al. High dose calcitriol (1,25(OH)2 vitamin D3) + dexamethasone in androgen independent prostate cancer (AIPC). Amer Soc Clin Oncol 19 337a (2000).
citation: Omdahl JL, Bobrovnikova EA, Choe S, Dwivedi PP, May BK. Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway. Steroids. 2001 Mar-May;66(3-5):381-9. doi: 10.1016/s0039-128x(00)00157-4.
PMID: 11179747
citation: Feldman D. Ketoconazole and other imidazole derivatives as inhibitors of steroidogenesis. Endocr Rev. 1986 Nov;7(4):409-20. doi: 10.1210/edrv-7-4-409. No abstract available.
PMID: 3536461
citation: Reinhardt TA, Horst RL. Ketoconazole inhibits self-induced metabolism of 1,25-dihydroxyvitamin D3 and amplifies 1,25-dihydroxyvitamin D3 receptor up-regulation in rat osteosarcoma cells. Arch Biochem Biophys. 1989 Aug 1;272(2):459-65. doi: 10.1016/0003-9861(89)90240-3.
PMID: 2546501
citation: Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889-95. doi: 10.1126/science.3283939.
PMID: 3283939
citation: Darwish HM, DeLuca HF. Recent advances in the molecular biology of vitamin D action. Prog Nucleic Acid Res Mol Biol. 1996;53:321-44. doi: 10.1016/s0079-6603(08)60149-x.
PMID: 8650307
citation: Christakos S, Raval-Pandya M, Wernyj RP, Yang W. Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3. Biochem J. 1996 Jun 1;316 ( Pt 2)(Pt 2):361-71. doi: 10.1042/bj3160361. Erratum In: Biochem J 1996 Sep 15;318(Pt 3):1079.
PMID: 8687373
citation: Darwish H, DeLuca HF. Vitamin D-regulated gene expression. Crit Rev Eukaryot Gene Expr. 1993;3(2):89-116.
PMID: 8391882
citation: Studzinski GP, McLane JA, Uskokovic MR. Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases. Crit Rev Eukaryot Gene Expr. 1993;3(4):279-312.
PMID: 8286848
citation: Weigel NL. Steroid hormone receptors and their regulation by phosphorylation. Biochem J. 1996 Nov 1;319 ( Pt 3)(Pt 3):657-67. doi: 10.1042/bj3190657.
PMID: 8920964
citation: Norman AW, Nemere I, Zhou LX, Bishop JE, Lowe KE, Maiyar AC, Collins ED, Taoka T, Sergeev I, Farach-Carson MC. 1,25(OH)2-vitamin D3, a steroid hormone that produces biologic effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):231-40. doi: 10.1016/0960-0760(92)90349-n.
PMID: 1314073
citation: Slater SJ, Kelly MB, Taddeo FJ, Larkin JD, Yeager MD, McLane JA, Ho C, Stubbs CD. Direct activation of protein kinase C by 1 alpha,25-dihydroxyvitamin D3. J Biol Chem. 1995 Mar 24;270(12):6639-43. doi: 10.1074/jbc.270.12.6639.
PMID: 7896803
citation: de Boland AR, Morelli S, Boland R. 1,25(OH)2-vitamin D3 signal transduction in chick myoblasts involves phosphatidylcholine hydrolysis. J Biol Chem. 1994 Mar 25;269(12):8675-9.
PMID: 8132595
citation: Khare S, Tien XY, Wilson D, Wali RK, Bissonnette BM, Scaglione-Sewell B, Sitrin MD, Brasitus TA. The role of protein kinase-C alpha in the activation of particulate guanylate cyclase by 1 alpha,25-dihydroxyvitamin D3 in CaCo-2 cells. Endocrinology. 1994 Jul;135(1):277-83. doi: 10.1210/endo.135.1.7912183.
PMID: 7912183
citation: de Boland AR, Norman A. Evidence for involvement of protein kinase C and cyclic adenosine 3',5' monophosphate-dependent protein kinase in the 1,25-dihydroxy-vitamin D3-mediated rapid stimulation of intestinal calcium transport, (transcaltachia). Endocrinology. 1990 Jul;127(1):39-45. doi: 10.1210/endo-127-1-39.
PMID: 2163320
citation: Gniadecki R. Activation of Raf-mitogen-activated protein kinase signaling pathway by 1,25-dihydroxyvitamin D3 in normal human keratinocytes. J Invest Dermatol. 1996 Jun;106(6):1212-7. doi: 10.1111/1523-1747.ep12348498.
PMID: 8752659
citation: MacDonald PN, Baudino TA, Tokumaru H, Dowd DR, Zhang C. Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription. Steroids. 2001 Mar-May;66(3-5):171-6. doi: 10.1016/s0039-128x(00)00200-2.
PMID: 11179724
citation: Barletta F, Freedman LP, Christakos S. Enhancement of VDR-mediated transcription by phosphorylation: correlation with increased interaction between the VDR and DRIP205, a subunit of the VDR-interacting protein coactivator complex. Mol Endocrinol. 2002 Feb;16(2):301-14. doi: 10.1210/mend.16.2.0764.
PMID: 11818502
citation: Zhang C, Dowd DR, Staal A, Gu C, Lian JB, van Wijnen AJ, Stein GS, MacDonald PN. Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. J Biol Chem. 2003 Sep 12;278(37):35325-36. doi: 10.1074/jbc.M305191200. Epub 2003 Jul 2.
PMID: 12840015
citation: Herdick M, Carlberg C. Agonist-triggered modulation of the activated and silent state of the vitamin D(3) receptor by interaction with co-repressors and co-activators. J Mol Biol. 2000 Dec 15;304(5):793-801. doi: 10.1006/jmbi.2000.4267.
PMID: 11124027
citation: Colston KW, Chander SK, Mackay AG, Coombes RC. Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol. 1992 Aug 18;44(4):693-702. doi: 10.1016/0006-2952(92)90405-8.
PMID: 1324683
citation: Frappart L, Falette N, Lefebvre MF, Bremond A, Vauzelle JL, Saez S. In vitro study of effects of 1,25 dihydroxyvitamin D3 on the morphology of human breast cancer cell line BT.20. Differentiation. 1989 Mar;40(1):63-9. doi: 10.1111/j.1432-0436.1989.tb00814.x.
PMID: 2545494
citation: Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SR. 1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Res. 1993 Aug 15;53(16):3712-8.
PMID: 8393379
citation: Mangelsdorf DJ, Koeffler HP, Donaldson CA, Pike JW, Haussler MR. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J Cell Biol. 1984 Feb;98(2):391-8. doi: 10.1083/jcb.98.2.391.
PMID: 6319426
citation: Godyn JJ, Xu H, Zhang F, Kolla S, Studzinski GP. A dual block to cell cycle progression in HL60 cells exposed to analogues of vitamin D3. Cell Prolif. 1994 Jan;27(1):37-46. doi: 10.1111/j.1365-2184.1994.tb01404.x.
PMID: 10465025
citation: Rigby WF, Noelle RJ, Krause K, Fanger MW. The effects of 1,25-dihydroxyvitamin D3 on human T lymphocyte activation and proliferation: a cell cycle analysis. J Immunol. 1985 Oct;135(4):2279-86.
PMID: 2993410
citation: Wang QM, Jones JB, Studzinski GP. Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. Cancer Res. 1996 Jan 15;56(2):264-7.
PMID: 8542578
citation: Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996 Jan 15;10(2):142-53. doi: 10.1101/gad.10.2.142.
PMID: 8566748
citation: Biggs JR, Kraft AS. Inhibitors of cyclin-dependent kinase and cancer. J Mol Med (Berl). 1995 Oct;73(10):509-14. doi: 10.1007/BF00198902.
PMID: 8581512
citation: Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995 May 15;9(10):1149-63. doi: 10.1101/gad.9.10.1149. No abstract available.
PMID: 7758941
citation: Sheikh MS, Rochefort H, Garcia M. Overexpression of p21WAF1/CIP1 induces growth arrest, giant cell formation and apoptosis in human breast carcinoma cell lines. Oncogene. 1995 Nov 2;11(9):1899-905.
PMID: 7478620
citation: Henkart PA. ICE family proteases: mediators of all apoptotic cell death? Immunity. 1996 Mar;4(3):195-201. doi: 10.1016/s1074-7613(00)80428-8. No abstract available.
PMID: 8624810
citation: Hockenbery DM. The bcl-2 oncogene and apoptosis. Semin Immunol. 1992 Dec;4(6):413-20.
PMID: 1286168
citation: Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh J. 1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 1996 Jul;58(4):367-76. doi: 10.1016/0960-0760(96)00055-6.
PMID: 8903420
citation: Xu HM, Tepper CG, Jones JB, Fernandez CE, Studzinski GP. 1,25-Dihydroxyvitamin D3 protects HL60 cells against apoptosis but down-regulates the expression of the bcl-2 gene. Exp Cell Res. 1993 Dec;209(2):367-74. doi: 10.1006/excr.1993.1322.
PMID: 8262155
citation: Henry HL. The 25(OH)D(3)/1alpha,25(OH)(2)D(3)-24R-hydroxylase: a catabolic or biosynthetic enzyme? Steroids. 2001 Mar-May;66(3-5):391-8. doi: 10.1016/s0039-128x(00)00158-6.
PMID: 11179748
citation: Miller GJ, Stapleton GE, Hedlund TE, Moffat KA. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res. 1995 Sep;1(9):997-1003.
PMID: 9816072
citation: Bareis P, Bises G, Bischof MG, Cross HS, Peterlik M. 25-hydroxy-vitamin d metabolism in human colon cancer cells during tumor progression. Biochem Biophys Res Commun. 2001 Jul 27;285(4):1012-7. doi: 10.1006/bbrc.2001.5289.
PMID: 11467853
citation: Zhao J, Tan BK, Marcelis S, Verstuyf A, Bouillon R. Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific. J Steroid Biochem Mol Biol. 1996 Feb;57(3-4):197-202. doi: 10.1016/0960-0760(95)00256-1.
PMID: 8645629
citation: Peehl DM, Seto E, Hsu JY, Feldman D. Preclinical activity of ketoconazole in combination with calcitriol or the vitamin D analogue EB 1089 in prostate cancer cells. J Urol. 2002 Oct;168(4 Pt 1):1583-8. doi: 10.1097/01.ju.0000030158.18335.84.
PMID: 12352462
citation: Ly LH, Zhao XY, Holloway L, Feldman D. Liarozole acts synergistically with 1alpha,25-dihydroxyvitamin D3 to inhibit growth of DU 145 human prostate cancer cells by blocking 24-hydroxylase activity. Endocrinology. 1999 May;140(5):2071-6. doi: 10.1210/endo.140.5.6698.
PMID: 10218956
citation: Strom M, Sandgren ME, Brown TA, DeLuca HF. 1,25-Dihydroxyvitamin D3 up-regulates the 1,25-dihydroxyvitamin D3 receptor in vivo. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9770-3. doi: 10.1073/pnas.86.24.9770.
PMID: 2481316
citation: Chen TL, Cone CM, Morey-Holton E, Feldman D. Glucocorticoid regulation of 1,25(OH)2-vitamin D3 receptors in cultured mouse bone cells. J Biol Chem. 1982 Nov 25;257(22):13564-9. No abstract available.
PMID: 6292196
citation: Levy J, Zuili I, Yankowitz N, Shany S. Induction of cytosolic receptors for 1 alpha, 25-dihydroxyvitamin D3 in the immature rat uterus by oestradiol. J Endocrinol. 1984 Mar;100(3):265-9. doi: 10.1677/joe.0.1000265.
PMID: 6321624
citation: Petkovich PM, Heersche JN, Tinker DO, Jones G. Retinoic acid stimulates 1,25-dihydroxyvitamin D3 binding in rat osteosarcoma cells. J Biol Chem. 1984 Jul 10;259(13):8274-80.
PMID: 6330107
citation: Reinhardt TA, Horst RL. Parathyroid hormone down-regulates 1,25-dihydroxyvitamin D receptors (VDR) and VDR messenger ribonucleic acid in vitro and blocks homologous up-regulation of VDR in vivo. Endocrinology. 1990 Aug;127(2):942-8. doi: 10.1210/endo-127-2-942.
PMID: 2164926
citation: Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 1995 Apr;16(2):200-57. doi: 10.1210/edrv-16-2-200. No abstract available.
PMID: 7781594
citation: Trump DL, Havlin KH, Messing EM, Cummings KB, Lange PH, Jordan VC. High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. J Clin Oncol. 1989 Aug;7(8):1093-8. doi: 10.1200/JCO.1989.7.8.1093.
PMID: 2474059
citation: OH WK. Secondary hormonal therapies in the treatment of prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):87-92; discussion 93. doi: 10.1016/s0090-4295(02)01581-9.
PMID: 12231058
citation: Hirst M, Feldman D. Glucocorticoids down-regulate the number of 1, 25-dihydroxyvitamin D3 receptors in mouse intestine. Biochem Biophys Res Commun. 1982 Apr 29;105(4):1590-6. doi: 10.1016/0006-291x(82)90970-6. No abstract available.
PMID: 6285911
citation: Kimberg DV, Baerg RD, Gershon E, Graudusius RT. Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest. 1971 Jun;50(6):1309-21. doi: 10.1172/JCI106610.
PMID: 4325312
citation: Haynes RC. Agents affecting calcification: calcium, parathyroid hormone, calcitonin, vitamin D, and other compounds. The Pharmacological Basis of Therapeutics. Gilman AG, Rall TW, Nies AS, Taylor P (eds). New York Pergamon Press 1496 (1990).
citation: Fakih M, Johnson CS, Trump DL. Glucocorticoids and treatment of prostate cancer: a preclinical and clinical review. Urology. 2002 Oct;60(4):553-61. doi: 10.1016/s0090-4295(02)01741-7. No abstract available.
PMID: 12385906
citation: Nishimura K, Nonomura N, Satoh E, Harada Y, Nakayama M, Tokizane T, Fukui T, Ono Y, Inoue H, Shin M, Tsujimoto Y, Takayama H, Aozasa K, Okuyama A. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst. 2001 Nov 21;93(22):1739-46. doi: 10.1093/jnci/93.22.1739.
PMID: 11717335
citation: Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. doi: 10.1200/JCO.1996.14.6.1756.
PMID: 8656243
citation: Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. doi: 10.1200/JCO.1999.17.8.2506.
PMID: 10561316
citation: Small EJ, Meyer M, Marshall ME, Reyno LM, Meyers FJ, Natale RB, Lenehan PF, Chen L, Slichenmyer WJ, Eisenberger M. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol. 2000 Apr;18(7):1440-50. doi: 10.1200/JCO.2000.18.7.1440.
PMID: 10735891
citation: Cunningham D, Gilchrist NL, Cowan RA, Forrest GJ, McArdle CS, Soukop M. Alfacalcidol as a modulator of growth of low grade non-Hodgkin's lymphomas. Br Med J (Clin Res Ed). 1985 Oct 26;291(6503):1153-5. doi: 10.1136/bmj.291.6503.1153.
PMID: 2996693
citation: Koeffler HP, Hirji K, Itri L. 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treat Rep. 1985 Dec;69(12):1399-407.
PMID: 2416438
citation: Rolla D, Paoletti E, Marsano L, Mulas D, Peloso G, Cannella G. Effects of subcutaneous calcitriol administration on plasma calcium and parathyroid hormone concentrations in continuous ambulatory peritoneal dialysis uremic patients. Perit Dial Int. 1993;13(2):118-21.
PMID: 8494932
citation: Davies M. High-dose vitamin D therapy: indications, benefits and hazards. Int J Vitam Nutr Res Suppl. 1989;30:81-6.
PMID: 2507709
citation: Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW, Trump DL. A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res. 1999 Jun;5(6):1339-45.
PMID: 10389917
citation: Beer TM, Munar M, Henner WD. A Phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation. Cancer. 2001 Jun 15;91(12):2431-9.
PMID: 11413535
citation: Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol. 2003 Jan 1;21(1):123-8. doi: 10.1200/jco.2003.05.117.
PMID: 12506180
citation: Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 1993 Sep 1;53(17):3976-85.
PMID: 8358726
citation: Paul A, Wilson S, Belham CM, Robinson CJ, Scott PH, Gould GW, Plevin R. Stress-activated protein kinases: activation, regulation and function. Cell Signal. 1997 Sep;9(6):403-10. doi: 10.1016/s0898-6568(97)00042-9.
PMID: 9376221
citation: Lewis TS, Shapiro PS, Ahn NG. Signal transduction through MAP kinase cascades. Adv Cancer Res. 1998;74:49-139. doi: 10.1016/s0065-230x(08)60765-4. No abstract available.
PMID: 9561267
citation: Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G. The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci. 2000 May;113 ( Pt 10):1661-70. doi: 10.1242/jcs.113.10.1661.
PMID: 10769197
citation: Yu WD, Chang MJ, Trump DL, Johnson CS. Interleukin-1alpha synergistic in vivo enhancement of cyclophosphamide- and carboplatin-mediated antitumor activity. Cancer Immunol Immunother. 1997 Aug;44(6):316-22. doi: 10.1007/s002620050388.
PMID: 9298933
citation: Kim D, Gregory CW, French FS, Smith GJ, Mohler JL. Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft. Am J Pathol. 2002 Jan;160(1):219-26. doi: 10.1016/S0002-9440(10)64365-9.
PMID: 11786415
citation: Gregory CW, Kim D, Ye P, D'Ercole AJ, Pretlow TG, Mohler JL, French FS. Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology. 1999 May;140(5):2372-81. doi: 10.1210/endo.140.5.6702.
PMID: 10218991
citation: Smitherman AB, Mohler JL, Maygarden SJ, Ornstein DK. Expression of annexin I, II and VII proteins in androgen stimulated and recurrent prostate cancer. J Urol. 2004 Feb;171(2 Pt 1):916-20. doi: 10.1097/01.ju.0000104674.70170.cd.
PMID: 14713853
citation: Smitherman AB, Gregory CW, Mohler JL. Apoptosis levels increase after castration in the CWR22 human prostate cancer xenograft. Prostate. 2003 Sep 15;57(1):24-31. doi: 10.1002/pros.10271.
PMID: 12886520
citation: Mohler JL, Morris TL, Ford OH 3rd, Alvey RF, Sakamoto C, Gregory CW. Identification of differentially expressed genes associated with androgen-independent growth of prostate cancer. Prostate. 2002 Jun 1;51(4):247-55. doi: 10.1002/pros.10086.
PMID: 11987153
citation: Kurahashi I, Matsunuma A, Kawane T, Abe M, Horiuchi N. Dexamethasone enhances vitamin D-24-hydroxylase expression in osteoblastic (UMR-106) and renal (LLC-PK1) cells treated with 1alpha,25-dihydroxyvitamin D3. Endocrine. 2002 Mar;17(2):109-18. doi: 10.1385/ENDO:17:2:109.
PMID: 12041912
citation: Akeno N, Matsunuma A, Maeda T, Kawane T, Horiuchi N. Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney. J Endocrinol. 2000 Mar;164(3):339-48. doi: 10.1677/joe.0.1640339.
PMID: 10694374
citation: Kang S, Li XY, Duell EA, Voorhees JJ. The retinoid X receptor agonist 9-cis-retinoic acid and the 24-hydroxylase inhibitor ketoconazole increase activity of 1,25-dihydroxyvitamin D3 in human skin in vivo. J Invest Dermatol. 1997 Apr;108(4):513-8. doi: 10.1111/1523-1747.ep12289736.
PMID: 9077483
citation: Schuster I, Egger H, Bikle D, Herzig G, Reddy GS, Stuetz A, Stuetz P, Vorisek G. Selective inhibition of vitamin D hydroxylases in human keratinocytes. Steroids. 2001 Mar-May;66(3-5):409-22. doi: 10.1016/s0039-128x(00)00159-8.
PMID: 11179750
citation: Sakaki T, Sawada N, Abe D, Komai K, Shiozawa S, Nonaka Y, Nakagawa K, Okano T, Ohta M, Inouye K. Metabolism of 26,26,26,27,27,27-F6-1alpha,25-dihydroxyvitamin D3 by CYP24: species-based difference between humans and rats. Biochem Pharmacol. 2003 Jun 15;65(12):1957-65. doi: 10.1016/s0006-2952(03)00190-4.
PMID: 12787875
citation: Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods. 2002 Feb;26(2):199-213. doi: 10.1016/S1046-2023(02)00023-3.
PMID: 12054897
citation: Kuo MH, Allis CD. In vivo cross-linking and immunoprecipitation for studying dynamic Protein:DNA associations in a chromatin environment. Methods. 1999 Nov;19(3):425-33. doi: 10.1006/meth.1999.0879.
PMID: 10579938
citation: Smith ML. Mdm2 sensitizes MCF7 breast cancer cells to cisplatin or carboplatin. Breast Cancer Res Treat. 1999 Nov;58(2):99-105. doi: 10.1023/a:1006390107197.
PMID: 10674873
citation: Fillippovich I, Sorokina N, Gatei M, Haupt Y, Hobson K, Moallem E, Spring K, Mould M, McGuckin MA, Lavin MF, Khanna KK. Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53. Oncogene. 2001 Jan 25;20(4):514-22. doi: 10.1038/sj.onc.1204118.
PMID: 11313982
citation: Mandic A, Viktorsson K, Molin M, Akusjarvi G, Eguchi H, Hayashi SI, Toi M, Hansson J, Linder S, Shoshan MC. Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner. Mol Cell Biol. 2001 Jun;21(11):3684-91. doi: 10.1128/MCB.21.11.3684-3691.2001.
PMID: 11340162
citation: Mabuchi S, Ohmichi M, Kimura A, Hisamoto K, Hayakawa J, Nishio Y, Adachi K, Takahashi K, Arimoto-Ishida E, Nakatsuji Y, Tasaka K, Murata Y. Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel. J Biol Chem. 2002 Sep 6;277(36):33490-500. doi: 10.1074/jbc.M204042200. Epub 2002 Jun 26.
PMID: 12087097
citation: Hisamoto K, Ohmichi M, Kanda Y, Adachi K, Nishio Y, Hayakawa J, Mabuchi S, Takahashi K, Tasaka K, Miyamoto Y, Taniguchi N, Murata Y. Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene analog LY117018 is differentially mediated by Akt and extracellular signal-regulated protein kinase in vascular endothelial cells. J Biol Chem. 2001 Dec 14;276(50):47642-9. doi: 10.1074/jbc.M103853200. Epub 2001 Oct 10.
PMID: 11595733
citation: Dent P, Grant S. Pharmacologic interruption of the mitogen-activated extracellular-regulated kinase/mitogen-activated protein kinase signal transduction pathway: potential role in promoting cytotoxic drug action. Clin Cancer Res. 2001 Apr;7(4):775-83. No abstract available.
PMID: 11309321
citation: Agoulnik IU, Krause WC, Bingman WE 3rd, Rahman HT, Amrikachi M, Ayala GE, Weigel NL. Repressors of androgen and progesterone receptor action. J Biol Chem. 2003 Aug 15;278(33):31136-48. doi: 10.1074/jbc.M305153200. Epub 2003 May 27.
PMID: 12771131
citation: Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129-56. doi: 10.1146/annurev.med.48.1.129.
PMID: 9046951
responsible party type: Sponsor-Investigator
investigator affiliation: Inova Health Care Services
investigator full name: Donald Trump, MD
investigator title: CEO & Executive Director, Inova Schar Cancer Institute
mesh term: Prostatic Neoplasms
mesh term: Vitamin D
mesh term: Calcitriol
mesh term: Ketoconazole
mesh term: Hydrocortisone
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and 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.
point of contact: 