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

Phase 1
Not Enrolling
Breast Cancer, Cancer, Carcinoma, Renal Cell, Lymphoma, Ovarian Cancer

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Trial Information

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

Inclusion Criteria

Biopsy proven advanced cancer, for whom no better therapy exists.

Enrollment of patients with breast cancer, lymphoma, renal cell cancer or ovarian cancer
are encouraged.

Patients with a life expectancy of at least 16 weeks, and a performance status (Karnofsky
Scale) of 70% or greater. No rapidly growing disease.

Patients with prior therapy.

WBC greater than 3,000/mm(3) and AGC greater than 1000/mm(3); platelets greater than

Creatinine clearance greater than 50 ml/min; bilirubin less than 1.5 mg/dl; SGOT less than
90 u/L; SGPT less than 100 u/L.

Patients must sign an informed consent and have geographic accessibility to return for
follow up and treatment.

No history of brain metastases.

No patients currently receiving treatment with the following agents or any other agent
known to significantly interact with cyclosporine, and the 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 patients with a history of coronary artery disease with angina pectoris or history of
congestive heart failure.

No patients with a history of cardiac disease, other than angina pectoris or congestive
heart failure, including patients with arrhythmias or conduction system abnormalities will
be considered on an individual basis.

No patients with symptomatic peripheral neuropathy (grade 2 or greater).

No patients with a positive serology for HIV.

No patients who are pregnant or unwilling to practice adequate contraception.

No patients with prior bone marrow transplantation or extensive irradiation resulting in
compromised bone marrow reserve.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 1994

Completion Date:

January 2001

Related Keywords:

  • Breast Cancer
  • Cancer
  • Carcinoma, Renal Cell
  • Lymphoma
  • Ovarian Cancer
  • Cyclosporine Analogue
  • Multidrug Resistance
  • Pgp Blocker
  • Pump Blocker
  • Taxol Over 90 Hours
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma, Renal Cell
  • Lymphoma
  • Ovarian Neoplasms



National Cancer Institute (NCI) Bethesda, Maryland  20892