A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer

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

Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled.

Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity.

Treatment continues every 28 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The Phase I clinical trial of the combination of 120-hour continuous intravenous infusion of vinblastine with oral PSC 833 has shown activity in patients with advanced malignancies, particularly renal cell cancer. The MTD of vinblastine in combination with the oral drink solution of PSC 833 was determined to be 0.9 mg/m2/day for five days and 12.5 mg/kg po q 12 hours for eight days, respectively. For the soft gel capsule formulation, the MTD was determined to be 0.6 mg/m2/day vinblastine for five days and 4 mg/kg po q 6 hours PSC 833 for eight days. Ataxia was the dose limiting toxicity. Of the 46 patients, two complete remissions and one partial remission were seen among 29 patients with renal cell carcinoma.

In this Phase I study, patients with advanced renal carcinoma will be treated with escalating doses of vinblastine given as a 72 hour infusion, starting at approximately 40% of the total standard dose. A shorter infusion schedule of vinblastine was chosen since there is evidence in other cytotoxic combinations that PSC 833 increases the AUC and decreases the plasma clearance of chemotherapeutic agents by approximately twofold. Cytochrome P 450 3A or CYP3A, which is the major cytochrome enzyme in the metabolism of vinblastine and PSC 833, will be measured during the first and fourth cycle through an in vivo test using a single intravenous dose of midazolam, a short-acting benzodiazepine. Vinblastine and PSC 833 pharmacokinetics will be performed at the same time. For patients with accessible lesions, tumor biopsy will be requested.

Study Type

Interventional

Enrollment

46

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically proven renal cancer with clear cell component:

Measurable or evaluable disease;

No brain metastases;

No grade 2 or greater peripheral neuropathy or neurologic toxicity symptoms.

PRIOR/CONCURRENT THERAPY:

Biologic Therapy: Not specified.

Chemotherapy: No prior or concurrent hypersensitivity to PSC 833 or cyclosporine A.

Endocrine Therapy: Not specified.

Radiotherapy: No prior radiation therapy within 4 weeks of study.

Surgery: No major surgery within 4 weeks of study.

Other: No concurrent treatments that interfere with cyclosporine blood concentrations.

PATIENT CHARACTERISTICS:

Age: 18 and over.

Performance Status: ECOG 0-2.

Life Expectancy: At least 16 weeks.

Hematopoietic:

ANC greater than or equal to 1500/mm(3);

Platelet count greater than or equal to 100,000/mm(3).

Hepatic:

Bilirubin no greater than 1.5 x normal;

AST no greater than 2.5 x normal.

Renal:

Creatinine no greater than 2.0 mg/dL OR;

Creatinine clearance greater than or equal to 50 mL/min.

Cardiovascular:

No concurrent angina or myocardial infarction that has not been appropriately treated.

Other:

Not pregnant or nursing.

Effective contraceptive required of all fertile patients.

Patients with a history of curatively treated basal cell or squamous cell carcinoma are eligible.

No HIV seropositivity.

No chronic hepatitis or cirrhosis.

Patients with concurrent reversible conditions such as diabetes, hypercalcemia, hyperuricemia, hyperviscosity, infection, renal disease, or spinal cord compression are eligible with appropriate therapy.

Patients must give written informed consent.

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

February 1, 1997

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

January 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 970074
  • 97-C-0074

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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