An Open-Label, Dose Escalation study of Paricalcitol (Zemplar TM) {19-NOR-1 ALPHA, 25-(OH)2 D2] in Combination with Gemcitabine (Gemzar) [2',2' Diflurodeoxycytidine] in patients with advanced Malignancies
Title An Open-Label, Dose Escalation study of Paricalcitol (Zemplar TM) {19-NOR-1 ALPHA, 25-(OH)2 D2] in Combination with Gemcitabine (Gemzar) [2',2' Diflurodeoxycytidine] in patients with advanced Malignancies
Contact HM
Principal Investigator Renuka Iyer, MD
Study Number 23204
Phase1
Summary This is a single institution, open label, dose escalation study of intravenous (i.v) paricalcitol (Zemplar TM) [19-nor-1 alpha, 25-(OH)2 D2] in combination with gemcitabine [2'2' diflurodeocycytidine] in patients with advanced malignancies. Weekly i.v. gemcitabine at a dose of 1000mg/m2 as a 100 minute infusion on a three weeks on and one week off schedule. Paricalcitol i.v. will be administered 24 hours prior to the gemcitabine infusion in escalating doses to MTD in separate cohorts of 3-6 patients. Paricalcitol dose escalation starting on week 2. Paricalcitol mg/kg, i.v. weekly, 24 hrs. prior to gemcitabine (0.72mcg/kg, 1.20 mcg/kg, 1.80mcg/kf, 2/4mcg/kg). Paricalcitol will be initiated on week 2 to allow assessment of gemcitabine pharmacokinetics on day 1 (pre paricalcitol) and day 8 (post paricalcitol). If one DLT is noted in a cohort of 3, more patients will be added at that dose level. Subsequent dose escalations will occur at 25% increments above the preceding dose in successive cohorts if toxicity is not encountered.
Eligibility
- Patients with advanced malignancies.
- Age >= 18 years.
- ECOG performance status <= 2 (Karnofsky >=60%, see Appendix B).
- Life expectancy of greater than 3 months.
- Patients must have normal organ and marrow function.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients who have had curative therapy for a condition associated with the risk of renal stones and who have been free of stone formulation for > 5 years or who have had a single episode of renal lithiasis over 5 years prior will be eligible.
- Absence of calculi in the urinary tract on KUB or other imaging studies before study entry.
