A Phase I, Dosage-finding and Pharmacokinetic Study of Intravenous Topotecan and Oral Erlotinib in Adults With Refractory Solid Tumors
The primary objectives of this trial include:
- To determine the maximum tolerated dosage (MTD) of intravenous topotecan when given in
combination with oral erlotinib.
- To define the dosage-limiting toxicities (DLT) of this combination.
- To evaluate the pharmacokinetic (PK) parameters of intravenous topotecan with and
The secondary objectives include:
- To evaluate the pharmacodynamic effect of the topotecan and erlotinib combination
- To evaluate for any correlations between the presence of CYP3A4/5 polymorphisms and
topotecan / erlotinib disposition and to measure the frequency of MDR1 and BCRP in
peripheral blood samples and correlate these results with topotecan pharmacokinetics
- To measure the frequency of UGT genotypes in peripheral blood samples
- To evaluate the objective response rate using the RECIST criteria.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dosage (MTD) of Intravenous Topotecan When Given in Combination With Oral Erlotinib
The MTD of topotecan was determined using a standard 3 + 3 dose escalation cohort design. The total sample and the number of patients who receive each dose in this design depends on the frequency of dose limiting toxicities (DLT) at each dosage. If 0 out of 3 patients experience a DLT at a given dosage level, 3 patients will be enrolled at the next dosage level. If greater than or equal to 2 patients experience a DLT at a given dosage level, dosage escalation will be stopped. If 1 out of 3 patients experience a DLT at a given dosage level, 3 patients are enrolled at the same dosage level.
MTD was assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21).
Lee S. Schwartzberg, MD, FACP
Accelerared Community Oncology Research Network, Inc.
United States: Institutional Review Board
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