Vinorelbine and XR9576 to Treat Cancer

Breast Cancer Clinical Trial

Official title: A Clinical Trial of the P-Glycoprotein Antagonist, XR9576, in Combination With Vinorelbine in Patients With Cancer: Analysis of the Interaction Between XR9576 and Vinorelbine

Status Completed

Clinical Trial Summary

Tumor resistance to anti-cancer drugs is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps chemotherapy drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called XR9576, has blocked pumping by this protein. It is being used in this study to try to increase the amount of the anti-cancer drug vinorelbine, in cancer cells. Vinorelbine has been shown in several clinical trials to be effective against some advanced cancers, including breast, lung and ovarian, and is one of the drugs pumped out of tumor cells by P-glycoprotein.

Patients with cancer 18 years and older may be eligible for this study. Candidates will be screened with tests that may include blood and urine tests, electrocardiogram, echocardiogram, CT scans, X-rays, and nuclear medicine studies. A tumor biopsy may be done for diagnostic or research purposes.

Study participants will undergo tumor imaging with the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures are taken with a gamma camera. After this baseline scan, patients will receive a dose of XR9576 and undergo a second scan 24 hours later. The scan will show whether XR9576 affects the accumulation and elimination of Sestamibi in tumor cells. This procedure may provide a way to monitor cancers for evidence of chemotherapy resistance and show if XR9576 can improve the effectiveness of therapy.

At least 10 days after the baseline and XR9576 scans, patients will begin the first of 3 or more 21-day cycles of vinorelbine treatment. On days 1 and 8 of each cycle, patients will receive a 30-minute infusion of XR9576 intravenously (through a vein) followed by vinorelbine, infused over a 6- to 10-minute period. (In some patients, XR9576 will be administered before only one of the two vinorelbine dosages.)

Physical examination, blood tests, and other procedures may be done periodically to monitor treatment.

Clinical Trial Description

Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies P-glycoprotein can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating P-glycoprotein antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. XR9576 is a new P-glycoprotein antagonist that is more potent, has prolonged activity, and is potentially devoid of significant pharmacokinetic interactions. This phase I study seeks to identify the safety of XR9576 administration in combination with vinorelbine and determine the extent, if any, of a pharmacokinetic interaction between these two drugs. Clinical responses will also be determined. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Cancer
• Lung Cancer
• Ovarian Cancer

• NCT number: NCT00001944
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: December 1999
• Completion date: June 2001