Trastuzumab and Flavopiridol in Treating Patients With Metastatic Breast Cancer

HER2-positive Breast Cancer Clinical Trial

Official title: A Phase I Study of Herceptin/Flavopiridol in HER-2 Positive Metastatic Breast Cancer

Status Terminated

Clinical Trial Summary

Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with flavopiridol may kill more tumor cells. Phase I trial to study the effectiveness of combining trastuzumab with flavopiridol in treating patients who have metastatic breast cancer

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of flavopiridol in combination with Herceptin in HER-2 positive metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To determine the dose of flavopiridol necessary to achieve a target plasma level of 300-500 nM of flavopiridol in combination with a fixed dose of Herceptin.

II. To assess the feasibility of measuring cyclin D1 in circulating tumor cells and tissue biopsies before and after therapy as a surrogate marker of flavopiridol activity.

III. To monitor target activity of flavopiridol and Herceptin in plasma, circulating tumor cells and tissue biopsies from breast cancer patients.

OUTLINE: This is a multicenter, dose-escalation study of flavopiridol.

Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose is determined (MTD). The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 10 patients receives flavopiridol at the MTD and trastuzumab on the once weekly schedule to assess the true toxicity rate. A second cohort of 10 patients receives flavopiridol at the MTD and trastuzumab once every 21 days to assess the tolerability of this schedule.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• HER2-positive Breast Cancer
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IV Breast Cancer

• NCT number: NCT00039455
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1
• Start date: April 2002