A Phase I Study to Evaluate MAG-CPT (PNU 166148) Given as One Single Intravenous Administration Every 4 Weeks in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the safety profile, maximum tolerated dose, and dose limiting
toxicities of PNU 166148 in patients with metastatic, refractory solid tumors. II. Define a
recommended dose of PNU 166148 for a Phase II study. III. Determine the pharmacokinetic
profile and molecular weight distribution of PNU 166148 and the pharmacokinetic profile of
free camptothecin in these patients. IV. Assess any evidence of antitumor activity in these
patients treated with this regimen.
OUTLINE: This is a dose escalation, open label, multicenter study. Patients receive PNU
166148 IV over 30 minutes. Treatment repeats every 4 weeks for 3-6 courses in the absence of
disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating
doses of PNU 166148 until the maximum tolerated dose (MTD) is determined. The MTD is defined
as the dose at which at least 2 of 3-6 patients experience dose limiting toxicity. Patients
are followed for 30 days, and then monthly thereafter only for resolution of adverse events
that occurred while on study and were attributable to study drug, unless another antitumor
treatment is begun.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study.
Primary Purpose: Treatment
Chris Twelves, MD, BMedSci, FRCP
University of Glasgow
United States: Federal Government