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Calcitriol, Ketoconazole, and Dexamethasone in Treating Patients With Metastatic or Unresectable Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00238225
Recruitment Status : Completed
First Posted : October 13, 2005
Last Update Posted : January 31, 2013
Information provided by:
Roswell Park Cancer Institute

Brief Summary:

RATIONALE: Calcitriol may cause solid tumor cells to look more like normal cells, and to grow and spread more slowly. Ketoconazole and dexamethasone may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with ketoconazole and dexamethasone may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of calcitriol when given together with ketoconazole and dexamethasone in treating patients with metastatic or unresectable solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Dietary Supplement: calcitriol Drug: dexamethasone Drug: ketoconazole Phase 1

Detailed Description:



  • Determine the maximum tolerated dose of calcitriol when administered with ketoconazole and dexamethasone in patients with metastatic or unresectable solid tumors.


  • Determine the tolerability and toxic effects of this regimen in these patients.
  • Determine tumor response in patients treated with this regimen.
  • Determine the pharmacokinetics of calcitriol and dexamethasone with or without ketoconazole in these patients.
  • Determine the pharmacodynamics of this regimen, in terms of CYP24 expression and activity and vitamin D receptor expression in peripheral blood mononuclear cells, in these patients.

OUTLINE: This is a dose-escalation study of calcitriol.

Patients receive oral dexamethasone twice daily beginning on day 0 and oral ketoconazole 3 times daily beginning on day 4. Patients also receive oral calcitriol once daily on days 1-3 of each week. Treatment continues 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.

After completion of study treatment, patients are followed for up to 30 days.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of Oral Calcitriol in Combination With Ketoconazole in Refractory Advanced Malignancies
Study Start Date : November 2004
Actual Primary Completion Date : June 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of calcitriol

Secondary Outcome Measures :
  1. Pharmacokinetics of calcitriol and dexamethasone with or without ketoconazole

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed solid tumor

    • Metastatic or unresectable disease
  • Standard curative or reliable palliative therapy is no longer effective OR does not exist
  • Brain metastases allowed provided they have been treated with surgery or radiotherapy AND are stable


Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months


  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Platelet count ≥ 75,000/mm^3


  • AST/ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal
  • No unstable or uncompensated hepatic disease


  • Creatinine ≤ 2 mg/dL
  • No unstable or uncompensated renal disease
  • No history of kidney, urethral, or bladder stones within the past 5 years


  • Ejection fraction ≥ 30%
  • No symptomatic congestive heart failure
  • No significant arrhythmias
  • No myocardial infarction within the past 3 months
  • No unstable angina pectoris
  • No unstable or uncompensated cardiac disease
  • No other significant heart disease


  • No unstable or uncompensated respiratory disease


  • No known severe hypersensitivity to ketoconazole or calcitriol or any of the excipients of these products
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study drugs
  • No ongoing or active infection


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
  • Able to receive oral medication
  • No sperm donation during and for ≥ 3 months after completion of study treatment
  • No evidence of significant clinical disorder or laboratory finding that would preclude study participation
  • No other severe or uncontrolled systemic disease
  • No psychiatric illness or social situation that would preclude study compliance


Biologic therapy

  • No concurrent prophylactic growth factors, including filgrastim (G-CSF) or sargramostim (GM-CSF)


  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

    • Any number of prior chemotherapy regimens allowed

Endocrine therapy

  • No concurrent systemic glucocorticoid therapy > physiologic replacement doses


  • See Disease Characteristics
  • Any number of prior radiotherapy regimens allowed


  • See Disease Characteristics
  • Recovered from prior major surgery
  • Concurrent surgery allowed provided ≥ 7 days has passed since the last dose of ketoconazole (ketoconazole may be restarted after adequate wound healing)


  • Recovered from prior anticancer therapy

    • Alopecia allowed
  • More than 30 days since prior nonapproved or investigational agents
  • More than 7 days since prior and no concurrent thiazides
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent digoxin or calcium supplementation
  • No concurrent proton pump inhibitor or H2 blockers
  • No concurrent medications that would alter the levels of ketoconazole and/or calcitriol, including the following:

    • Phenytoin
    • Carbamazepine
    • Barbiturates (e.g., phenobarbital)
    • Rifampin
    • Hypericum perforatum (St. John's wort)
  • No concurrent drugs that would be significantly impaired in a clinically important way by ketoconazole
  • No other concurrent investigational or commercial agents or therapies for this malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00238225

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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
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Principal Investigator: Donald L. Trump, MD Roswell Park Cancer Institute

Layout table for additonal information Identifier: NCT00238225     History of Changes
Other Study ID Numbers: I 33204
First Posted: October 13, 2005    Key Record Dates
Last Update Posted: January 31, 2013
Last Verified: January 2013
Keywords provided by Roswell Park Cancer Institute:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Cytochrome P-450 CYP3A Inhibitors
Calcium-Regulating Hormones and Agents
Calcium Channel Agonists
Membrane Transport Modulators
Vasoconstrictor Agents