Calcitriol, Ketoconazole, and Hydrocortisone in Treating Patients With Advanced or Recurrent Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Roswell Park Cancer Institute
Information provided by (Responsible Party):
Roswell Park Cancer Institute Identifier:
First received: September 27, 2007
Last updated: February 3, 2015
Last verified: February 2015

RATIONALE: Calcitriol may help prostate cancer cells become more like normal cells and grow and spread more slowly. Ketoconazole may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with ketoconazole and hydrocortisone may be an effective treatment for prostate cancer.

PURPOSE: This phase I/II trial is studying the side effects and best dose of calcitriol when given together with ketoconazole and hydrocortisone and to see how well it works in treating patients with advanced or recurrent prostate cancer.

Condition Intervention Phase
Prostate Cancer
Dietary Supplement: calcitriol
Drug: ketoconazole
Drug: therapeutic hydrocortisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Oral Calcitriol in Combination With Ketoconazole in Androgen Independent Prostate Cancer

Resource links provided by NLM:

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose of calcitriol (phase I) [ Time Frame: In 4 week cycles ] [ Designated as safety issue: Yes ]
  • Prostate-specific antigen response rate (complete and partial) (phase II) [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as measured by NCI CTC version 3.0 [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
  • Objective tumor response as measured by monthly physical exam and radiographic evaluation every 12 weeks [ Time Frame: Monthly and at 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: October 2006
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dose-escalation of calcitriol)

PHASE I: Patients receive calcitriol PO QD on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO BID on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dietary Supplement: calcitriol
Drug: ketoconazole
Given Orally
Drug: therapeutic hydrocortisone
Given Orally

Detailed Description:



  • To determine the maximum tolerated dose (MTD) of oral calcitriol when given together with ketoconazole and hydrocortisone in patients with advanced or recurrent androgen-independent prostate cancer. (Phase I)
  • To estimate the prostate-specific antigen response rate. (Phase II)


  • To evaluate the pharmacokinetics of the phase II dose of calcitriol with and without ketoconazole.
  • Describe any objective tumor responses to the combination of calcitriol, ketoconazole, and hydrocortisone among patients with measurable disease using RECIST criteria.
  • Explore the pharmacodynamic effects of this combination in peripheral blood mononuclear cells.
  • Determine toxicities and tolerability of this regimen.

OUTLINE: This is a phase I, dose-escalation study of calcitriol followed by a phase II study.

  • Phase I: Patients receive oral calcitriol once daily on days 1-3, 8-10, 15-17, and 22-24, oral ketoconazole three times daily on days 1-28, and oral hydrocortisone twice daily on days 0-28 of course 1 and days 1-28 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of calcitriol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive oral calcitriol at the MTD determined in phase I on days 1-3, 8-10, 15-17, and 22-24, oral ketoconazole three times daily on days 4-28, and oral hydrocortisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Peripheral blood mononuclear cells are collected periodically to evaluate the pharmacodynamics of calcitriol, hydrocortisone, and ketoconazole. Some patients undergo blood collection on days 1 and 15 for calcitriol pharmacokinetic studies.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed androgen-independent adenocarcinoma of the prostate

    • Advanced or recurrent disease for which standard curative or reliable palliative therapy does not exist or is no longer effective
  • Measurable disease with elevated prostate-specific antigen (PSA) or evaluable disease (PSA elevation will constitute evaluable disease)
  • Patients who have received prior antiandrogens or progestational agents as therapy for prostate cancer must discontinue therapy and demonstrate a rising PSA ≥ 28 days* after discontinuation NOTE: *At least 42 days for bicalutamide or nilutamide
  • Patients undergoing androgen deprivation using luteinizing hormone-releasing hormone (LHRH) analogues must continue therapy or undergo orchiectomy to maintain castrate levels of testosterone
  • Patients with brain metastases which are stable and have been treated for surgery or irradiation are eligible


  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • Leukocytes ≥ 3,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Total bilirubin normal
  • AST/ALT ≤ 2.5 x upper limit of normal
  • Creatinine ≤ 2 mg/dL
  • Calcium normal
  • Must be able to receive oral medications, including oral capsules
  • No known severe hypersensitivity to ketoconazole, calcitriol, or any of the excipients of these products
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to calcitriol, ketoconazole, or other agents used in the study
  • No evidence of any other significant clinical disorder or laboratory finding that would make it undesirable for the patient to participate in the trial
  • No history of kidney, ureteral, or bladder stones within the past 5 years
  • No incomplete healing from prior oncologic treatments or other major surgery
  • No unresolved chronic toxicity > grade 2
  • No heart failure or significant heart disease, including any of the following:

    • Significant arrhythmias
    • Myocardial infarction within the past 3 months
    • Unstable angina pectoris
    • Documented ejection fraction < 30%
  • No other severe or uncontrolled systemic disease (e.g., unstable or compensated respiratory, cardiac, hepatic, or renal disease) or intercurrent illness including, but not limited to any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Psychiatric illness/social situation that would limit compliance with study requirements


  • See Disease Characteristics
  • Recovered from prior anticancer therapy
  • At least 7 days since prior thiazide therapy
  • At least 30 days since prior treatment with a non-approved or investigational drug or agent
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 4 weeks since prior radiotherapy or cytotoxic therapy
  • No more than 2 prior cytotoxic chemotherapy regimens

    • Retinoids, vitamin D analogues, PPARγ agonists or antagonists, antiandrogens, progestational agents, estrogens, PC-SPES, LHRH analogues, vaccines, and cytokines are not considered cytotoxics
    • Prior ketoconazole and glycocorticoids allowed
  • Concurrent megestrol acetate for hot flashes at a dose of ≤ 40 mg/day allowed
  • No concurrent digoxin therapy
  • No concurrent systemic glucocorticoid therapy at greater than physiologic replacement doses
  • No concurrent calcium supplementation
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent proton pump inhibitors or H2 blockers
  • No concurrent use of any of the following:

    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Rifampicin
    • Phenobarbital
    • Hypericum perforatum (St. John wort)
    • Alfentanil
    • Alfuzosin
    • Almotriptan
    • Alprazolam
    • Amiodarone
    • Amitriptyline
    • Aprepitant
    • Amprenavir
    • Aripiprazole
    • Bepridil
    • Bortezomib
    • Bosentan
    • Budesonide
    • Buprenorphine
    • Buspirone
    • Cilostazol
    • Cisapride
    • Cyclosporine
    • Delavirdine
    • Didanosine
    • Digoxin
    • Disopyramide dofetilide
    • Donepezil
    • Eletriptan
    • Eplerenone
    • Fluticasone
    • Fosamprenavir
    • Galantamine
    • Systemic griseofulvin
    • Indinavir
    • Levobupivacaine
    • Lopinavir
    • Midazolam
    • Mifepristone
    • Modafinil
    • Nateglinide
    • Nefazodone
    • Nelfinavir
    • Oxcarbazepine
    • Pimozide
    • Quetiapine
    • Quinidine
    • Repaglinide
    • Rifabutin
    • Rifampin
    • Rifapentine
    • Ritonavir
    • Saquinavir
    • Valdecoxib
    • Vardenafil
    • Ziprasidone
    • Statins
    • Calcium channel blockers
    • Macrolides
    • Sildenafil
    • Sirolimus
    • Tacrolimus
    • Tadalafil
    • Tolterodine
    • Theophyllines
    • Triazolam
    • Zonisamide
    • Other agents that would be significantly perturbed in a clinically important way by the P450 inhibitory properties of ketoconazole
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00536991

United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263-0001
Contact: AskRPCI    877-275-7724   
Sponsors and Collaborators
Roswell Park Cancer Institute
Principal Investigator: Saby George, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute Identifier: NCT00536991     History of Changes
Other Study ID Numbers: I 68905, RPCI-I-68905
Study First Received: September 27, 2007
Last Updated: February 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
adenocarcinoma of the prostate
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Neoplasms by Site
Urogenital Neoplasms
Hydrocortisone 17-butyrate 21-propionate
Genital Diseases, Male
Prostatic Diseases
Cortisol succinate
Hydrocortisone acetate
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Anti-Inflammatory Agents
Antifungal Agents
Bone Density Conservation Agents
Calcium Channel Agonists
Cardiovascular Agents
Dermatologic Agents
Enzyme Inhibitors
Growth Substances
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on July 01, 2015