A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma
I. To determine the safety and toxicity profile of UCN-01 when given in combination with
gemcitabine to patients with unresectable or metastatic adenocarcinoma of the pancreas.
II. To characterize the pharmacokinetic profiles of gemcitabine and UCN-01 when given in
combination and to correlate various measurements of UCN-01 with intracellular
III. To determine recommended doses of UCN-01 and gemcitabine in combination to be used in a
planned subsequent phase II trial.
I. To record the frequency, extent, and duration of any tumor responses. II. To correlate
serum alpha-1 acid glycoprotein (AGP) levels with UCN-01 pharmacokinetics and toxicity.
OUTLINE: This is a dose-escalation study.
Patients receive gemcitabine IV over 1-2 hours on days 1 and 8 followed by UCN-01 IV over 3
hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity. Sequential dose escalation of UCN-01 is followed by sequential dose
escalation of gemcitabine.
Cohorts of 3-6 patients receive escalating doses of UCN-01 and then gemcitabine until the
maximum tolerated dose (MTD) of the combination 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. Once the MTD is determined, at least 6 patients are treated at the recommended
phase II dose.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of toxicity
Up to 4 years
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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