Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery
Adult Solid Neoplasm
Dietary Supplement: Calcitriol
Drug: Gemcitabine Hydrochloride
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial of Oral Calcitriol With Fixed Dose of Cisplatin and Gemcitabine in Patients With Advanced Solid Tumors|
- MTD of oral calcitriol when combined with a standard dose of gemcitabine hydrochloride and cisplatin, determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]A standard 3+3 with de-escalation will be used to estimate the MTD.
- Toxicity of this combination, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]Tabulated overall or by dose level (as appropriate).
- Pharmacokinetic (PK) analyses of calcitriol at the MTD in an expanded cohort of 6 patients, including peak levels, area under the concentration-time curve from time 0-72 hours, terminal half-life, volume of distribution, and total body clearance [ Time Frame: Days 1-3 of course 1 ] [ Designated as safety issue: No ]PK data will be presented as plots of serum calcitriol concentration over time for each patient. An assessment of whether systemic calcitriol exposure associated with antitumor activity in preclinical models is achieved in these patients will be made.
- Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Responses tabulated as appropriate.
|Study Start Date:||September 2011|
|Study Completion Date:||November 2015|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)
Patients receive calcitriol PO on days 1, 2, 8, 9, 15 and 16; cisplatin IV over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dietary Supplement: Calcitriol
Other Names:Drug: Cisplatin
Given IVDrug: Gemcitabine Hydrochloride
Other Names:Other: Pharmacological Study
Other Name: pharmacological studies
I. To determine the maximum tolerated dose of oral calcitriol when combined with a standard dose of gemcitabine (gemcitabine hydrochloride) and cisplatin in a 28-day cycle.
I. Describe the toxicity of this combination using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
II. Study the pharmacokinetics of calcitriol at the maximum tolerated dose (MTD) in an expanded cohort of 6 patients.
III. Describe the clinical activity associated with this regimen in this advanced solid tumor population.
Patients receive calcitriol orally (PO) on days 1, 2, 8, 9, 15 and 16; cisplatin intravenously (IV) over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01093092
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Virginia|
|Emily Couric Clinical Cancer Center|
|Charlottesville, Virginia, United States, 22903|
|Principal Investigator:||Grace Dy||Roswell Park Cancer Institute|