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A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833

Phase 1
Not Enrolling
Breast Cancer, Kidney Neoplasm, Lymphoma, Neoplasm Metastasis, Ovarian Cancer

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Trial Information

A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833

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.

Inclusion Criteria

Biopsy proven metastatic cancer, for whom no better therapy exists. All patients are
eligible. Enrollment of patients with kidney, breast, ovarian cancers, and lymphomas is

A life expectancy of at least 16 weeks, and a performance status (Karnofsky scale) of 70%
or greater. Patients without rapidly growing disease.

Any prior therapy except for previous bone marrow transplantation.

WBC greater than 3,000/mm3 and ACG greater than 1,000/mm3; platelets greater than

Creatinine Clearance greater than 50 ml/min; bilirubin less than 1.5 mg/dl; SGOT less than
70u/L; SGPT less than 80u/L.

A signed informed consent and geographic accessibility for the patient to return for
follow up and treatment.

No history of brain metastases.

Not currently receiving treatment with the following agents or any other agent known to
significantly interact with cyclosporine, and treatment cannot be discontinued, or changed
to another therapeutically equivalent allowable drug: acetazolamide, barbiturates,
corticosteroids, diltiazem, erythromycin, fluconazole, ketoconazole, nicardipine,
phenothiazines, phenytoin, rifampin, sulfonamides, trimethoprim, verapamil, tamoxifen,
progesterone, quinine, quinidine, or amiodarone.

No symptomatic peripheral neuropathy (grade 2 or greater arising from prior vinca alkaloid

No positive serology for HIV.

No ongoing pregnancy or unwillingness to practice adequate contraception.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

September 1992

Completion Date:

June 2002

Related Keywords:

  • Breast Cancer
  • Kidney Neoplasm
  • Lymphoma
  • Neoplasm Metastasis
  • Ovarian Cancer
  • Vinblastine
  • Multidrug Resistance
  • Resistance Reversal
  • Pgp Blocker
  • Pharmacokinetics
  • Cyclosporine
  • Drug Interactions
  • Breast Neoplasms
  • Neoplasms
  • Kidney Neoplasms
  • Lymphoma
  • Neoplasm Metastasis
  • Ovarian Neoplasms



National Cancer Institute (NCI) Bethesda, Maryland  20892