Calcitriol, Ketoconazole, and Dexamethasone in Treating Patients With Metastatic or Unresectable Solid Tumors
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.
|Unspecified Adult Solid Tumor, Protocol Specific||Dietary Supplement: calcitriol Drug: dexamethasone Drug: ketoconazole||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Study of Oral Calcitriol in Combination With Ketoconazole in Refractory Advanced Malignancies|
- Maximum tolerated dose (MTD) of calcitriol
- Pharmacokinetics of calcitriol and dexamethasone with or without ketoconazole
|Study Start Date:||November 2004|
|Primary Completion Date:||June 2006 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00238225
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Principal Investigator:||Donald L. Trump, MD||Roswell Park Cancer Institute|