Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00238225
First received: October 12, 2005
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Dietary Supplement: calcitriol
Drug: dexamethasone
Drug: ketoconazole
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study of Oral Calcitriol in Combination With Ketoconazole in Refractory Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of calcitriol [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of calcitriol and dexamethasone with or without ketoconazole [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: November 2004
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months

Hematopoietic

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

Hepatic

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

Renal

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

Cardiovascular

  • 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

Pulmonary

  • No unstable or uncompensated respiratory disease

Immunologic

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • 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)

Other

  • 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
  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 ClinicalTrials.gov identifier: NCT00238225

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

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00238225     History of Changes
Other Study ID Numbers: I 33204, RPCI-I-33204
Study First Received: October 12, 2005
Last Updated: January 30, 2013
Health Authority: United States: Federal Government

Keywords provided by Roswell Park Cancer Institute:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
BB 1101
Calcitriol
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Ketoconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Bone Density Conservation Agents
Calcium Channel Agonists
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Membrane Transport Modulators
Micronutrients
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014