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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001570
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
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.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose

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.


Condition Intervention Phase
Kidney Neoplasms Neoplasm Metastasis Drug: PSC 833 Drug: vinblastine Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 46
Study Start Date: February 1997
Estimated Study Completion Date: January 2001
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.

  Eligibility

Information from the National Library of Medicine

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

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.

  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00001570


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

Publications:
ClinicalTrials.gov Identifier: NCT00001570     History of Changes
Other Study ID Numbers: 970074
97-C-0074
First Submitted: November 3, 1999
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
Last Verified: January 2000

Keywords provided by National Institutes of Health Clinical Center (CC):
Cytochrome P 450
Multi-Drug Resistance
P-Glycoprotein
Pharmacokinetics

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Kidney Neoplasms
Carcinoma, Renal Cell
Neoplastic Processes
Pathologic Processes
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vinblastine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action