Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer
RATIONALE: Paricalcitol may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving paricalcitol together with gemcitabine may be an effective treatment for cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of paricalcitol when given together with gemcitabine in treating patients with advanced cancer.
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: gemcitabine hydrochloride Drug: paricalcitol||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||An Open Label, Dose Escalation Study of Paricalcitol (Zemplar™) [19-NOR-1 ALPHA, 25-(OH) D] in Combination With Gemcitabine [2', 2' -Difluorodeoxycytidine] in Patients With Advanced Malignancies|
- To determine the maximum tolerated dose (MTD) of i. v. pancalcitol given weekly, in combination with fixed dose rate infusion of i. v.gemcitabine given weekly in patients with advanced malignancies. [ Time Frame: 4 weeks ]
- To assess toxicity. [ Time Frame: 8 week intervals ]
- To determine the effects of paricalcitol on the pharmacokinetics of gemcitabine. [ Time Frame: Days 1 & 8, cycle 1 ]
- To determine the effects of pariclcitol on cytidine deaminase in PBM [ Time Frame: Days 1 & 8, cycle 1 ]
- To determine the effects of paricalcitol on dFdCTP in PBM [ Time Frame: Days 1 & 8, cycle 1 ]
- To determine the pharmacokinetics of paricalcitol when given with gemcitabine [ Time Frame: Day 7, cycle 1 ]
- To describe clinical outcome for response and survival [ Time Frame: 8 week intervals ]
|Study Start Date:||August 2004|
|Study Completion Date:||September 2014|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Paricalcitol IV in combination with Gemcitabine IV
Patients receive gemcitabine hydrochloride IV over 80 minutes on days 1, 8, and 15 and paricalcitol IV over 15 minutes on days 7 and 14 in course 1. Beginning in course 2, patients receive paricalcitol IV over 15 minutes on days 1, 8, and 15 and gemcitabine hydrochloride IV over 80 minutes on days 2, 9, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IVDrug: paricalcitol
- Determine the maximum tolerated dose (MTD) of paricalcitol when given with gemcitabine in patients with advanced malignancy.
- Determine safety and toxicity of this regimen in these patients.
- Determine the pharmacokinetics of these regimens in these patients.
- Determine the clinical outcome (overall survival and best overall response) of patients treated with this regimen.
OUTLINE: This is a dose-escalation, open-label study.
Patients receive gemcitabine IV over 80 minutes on days 1, 8, and 15 and paricalcitol IV over 15 minutes on days 7 and 14 in course 1. Beginning in course 2, patients receive paricalcitol IV over 15 minutes on days 1, 8, and 15 and gemcitabine IV over 80 minutes on days 2, 9, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of paricalcitol 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. A minimum of 6 patients are treated at the MTD.
After completion of study treatment, patients are followed for survival.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217477
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Principal Investigator:||Renuka Iyer, MD||Roswell Park Cancer Institute|