A Phase I Study of Triapine® in Combination With Radiation Therapy in Locally Advanced Pancreas Cancer
I. To determine the maximal tolerable dose (MTD) of 3-AP administered in combination with
radiation therapy (XRT) in patients with locally advanced pancreatic carcinomas.
I. To document the therapeutic response of this combination in patients with locally
advanced pancreatic carcinomas.
II. To establish radiographic correlates using secretin stimulated magnetic resonance
cholangiopancreatography (MRCP) and dynamic contrast enhanced magnetic resonance imaging
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 triapine.
OUTLINE: This is a dose-escalation study of 3-AP (Triapine®). Patients undergo radiotherapy
once daily, 5 days a week, for approximately 5½ weeks (a total of 28 fractions).
Patients also receive 3-AP (Triapine®) IV over 2 hours 3 days a week every other week for 5½
weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
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
at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients
are treated at the MTD. After completion of study treatment, patients are followed monthly
for 1 year.
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 will be the dose at which 1 or fewer patients (less than or equal to 1/6) experiences a DLT during the treatment cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing DLT. DLT will be defined as greater than or equal to Grade 3 non-hematologic or greater than or equal to Grade 4 hematologic adverse event with the following exceptions: greater than or equal to Grade 3 nausea and greater than or equal to Grade 3 vomiting that improves with antiemetic therapy greater than or equal to Grade 3 diarrhea that improves with Lomotil.
Observed clinically for 3-4 hours after each 3-AP infusion during the first week of treatment
Ohio State University
United States: Food and Drug Administration
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