A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833
Status:
Completed
Trial end date:
2002-06-01
Target enrollment:
Participant gender:
Summary
The clinical study entitled "A Phase I Study of Infusional Chemotherapy with the
P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for a
proposed P-glycoprotein antagonist, PSC 833. 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 vinblastine, and to determine how the drug affects the pharmacokinetics of vinblastine.
PSC 833 will most likely reduce the clearance of vinblastine, as reported for the parent
compound, cyclosporine. This effect will increase the area under the curve (AUC) of
vinblastine, may increase toxicity, and requires that the escalation scheme for PSC 833 be a
conservative one. Initially, a 120 hour infusion of vinblastine will be given alone. Then 8
days of PSC 833 will follow to allow monitoring of adverse effects of PSC 833 alone. This
first cycle of vinblastine will be given in the absence of PSC 833; in second and subsequent
cycles 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.