A Phase I Study of Herceptin/Flavopiridol in HER-2 Positive Metastatic Breast Cancer
I. To evaluate the safety and tolerability of flavopiridol in combination with Herceptin in
HER-2 positive metastatic breast cancer.
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
PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|