A Phase I Study of Infusional Paclitaxel With the P-Glycoprotein Antagonist PSC 833
The clinical study entitled "A Phase I Study of Infusional Paclitaxel with the
P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for the
proposed P-glycoprotein antagonist, PSC 833, in combination with paclitaxel. PSC 833 is a
cyclosporine analogue which is purportedly non-nephrotoxic and non-immunosuppressive. It
has been shown in in vitro studies to enhance chemosensitivity as well as cyclosporine and
to be far better at increasing intracellular drug accumulation than the concentrations of
verapamil which are clinically achievable. The purpose of this study is to define the
maximum tolerated dose in combination with paclitaxel, and to determine how the drug affects
the pharmacokinetics of paclitaxel. PSC 833 will most likely reduce the clearance of
paclitaxel as reported for the parent compound, cyclosporine. This effect will increase the
area under the curve (AUC) of paclitaxel, may increase toxicity, and requires that the
escalation scheme for PSC 833 be a conservative one. The first cycle of paclitaxel will be
given in the absence of PSC 833. Subsequently, 7 days of PSC 833 will be given alone to
allow monitoring of pharmacokinetics and adverse effects of PSC 833 alone. In the second
cycle, both agents will be combined. Escalation of the PSC 833 will continue until a target
concentration is reached, or until the maximum tolerated dose is reached. Clinical
responses will be monitored in order to provide the best possible medical care to our
patients.
Interventional
Endpoint Classification: Safety Study, Primary Purpose: Treatment
United States: Federal Government
940119
NCT00001383
March 1994
January 2001
Name | Location |
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National Cancer Institute (NCI) | Bethesda, Maryland 20892 |