A Phase I Study of a Prolonged Infusion of Triapine in Combination With a Fixed Dose Rate of Gemcitabine in Patients With Advanced Solid Tumors and Lymphomas
I. To determine the maximal tolerable dose (MTD) of 3-AP administered as a 24 hour infusion
in combination with and fixed-dose gemcitabine hydrochloride (GEM) in patients with advanced
solid tumors or lymphomas.
I. To define the qualitative and quantitative toxicities of the 3-AP/GEM combination in
regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of this combination in those patients when
III. To measure deoxycytidine triphosphate (dCTP) levels in peripheral blood mononuclear
cells (PBMCs) before and after treatment at specified times and try to correlate findings to
activity and toxicity of 3-AP.
IV. To perform limited pharmacokinetic analysis.
OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).Patients receive 3-AP
(Triapine®) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes
on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease
progression or unacceptable toxicity.
Patients achieving complete response (CR) receive 1 additional course of therapy beyond
documented CR.Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) 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 periodically for 2 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
MTD is the maximum dose level with fewer than 2 of 3/6 patients experiencing DLT. The study uses standard method phase I design of dose escalation. DLT will be defined as greater or equal to Grade 3 non-hematologic or greater or equal to Grade 4 hematologic adverse event EXCEPT: greater or equal to Grade 3 nausea and greater or equal to Grade 3 vomiting that improves with antiemetic therapy; greater or equal to Grade 3 diarrhea that improves with Lomotil; and greater or equal to Grade 4 Neutropenia that recovers to less or equal to Grade 3 within 7 days of first identification.
Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|