Phase I Trial of Doxorubicin and Alvocidib (Flavopiridol; NCI Supplied Agent, NSC 649890) in the Treatment of Metastatic Sarcoma
I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with a
fixed dose of doxorubicin (doxorubicin hydrochloride) in patients with unresectable
metastatic or locally recurrent sarcoma.
I. Determine the clinical pharmacokinetics of this regimen in these patients. II. Determine,
preliminarily, the therapeutic activity of this regimen in these patients.
III. Correlate pRb, p53, and p21 protein levels with treatment response and apoptosis in
patients treated with this regimen.
IV. Correlate NMR biochemical patterns with response in patients treated with this regimen.
OUTLINE: This is an open-label, dose-escalation study of alvocidib.
Patients receive doxorubicin hydrochloride intravenously (IV) over 5-10 minutes and
alvocidib IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Patients reaching a cumulative doxorubicin dose of 600
mg/m^2 or experiencing cardiotoxicity may receive alvocidib alone at the discretion of the
investigator. Cohorts of 3-6 patients receive escalating doses of alvocidib until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Ten additional patients
receive treatment at the MTD. Patients are followed every 3 months for 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of alvocidib when given every three weeks in conjunction with doxorubicin hydrochloride
Defined as the dose level immediately preceding the dose where 2 or more patients experienced DLT.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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