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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001383
Recruitment Status : Completed
First Posted : December 10, 2002
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This is a dosage escalation study to estimate the maximum tolerated dose of drug resistance inhibitor PSC 833 given in combination with paclitaxel. Groups of 3 to 6 patients receive continuous-infusion paclitaxel for 5 days and oral PSC 833 for 6-7 days, following paclitaxel on the first course, then beginning 3 days prior to paclitaxel on subsequent courses.

Stable and responding patients are re-treated every 21 days, with paclitaxel dose adjusted to maintain an absolute neutrophil count less than 500 for no more than 4 days.

Condition or disease Intervention/treatment Phase
Breast Cancer Cancer Carcinoma, Renal Cell Lymphoma Ovarian Cancer Drug: PSC 833 Drug: paclitaxel Phase 1

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 52 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of Infusional Paclitaxel With the P-Glycoprotein Antagonist PSC 833
Study Start Date : March 1994
Study Completion Date : January 2001

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 100,000/mm(3).

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001383

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United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)

Layout table for additonal information Identifier: NCT00001383    
Other Study ID Numbers: 940119
First Posted: December 10, 2002    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: March 2000
Keywords provided by National Institutes of Health Clinical Center (CC):
Cyclosporine Analogue
Multidrug Resistance
Pgp Blocker
Pump Blocker
Taxol Over 90 Hours
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms by Site
Urogenital Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents