A Phase 1 Study of Alvocidib (Flavopiridol) in Combination With Radiation in Locally Advanced, Non-Operable Pancreatic and Extrahepatic Bile Duct Cancers
I. Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy
followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.
II. Determine the toxicity of this regimen in these patients.
I. Determine the pharmacokinetics of flavopiridol in these patients. II. Determine,
preliminarily, the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of flavopiridol.
Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5)
for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5
weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning
within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive
gemcitabine hydrochloride alone or in combination with another cytotoxic agent or
gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at
the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential
curative resection are referred for a surgical evaluation before initiating gemcitabine
hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol
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. Once
the MTD is determined, 10 additional patients are treated at the recommended phase II dose.
Patients are followed at 4 weeks and then every 8 weeks thereafter.
PROJECTED ACCRUAL: Approximately 3-46 patients will be accrued for this study within 2
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of flavopiridol when administered biweekly in conjunction with radiation for patients with locally advanced pancreatic or extrahepatic bile duct cancer
Gary K. Schwartz
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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