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

March 3, 2008 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

52

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute (NCI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1994

Study Completion

January 1, 2001

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

December 9, 2002

First Posted (ESTIMATE)

December 10, 2002

Study Record Updates

Last Update Posted (ESTIMATE)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

March 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 940119
  • 94-C-0119

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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