A Phase II Study of Erlotinib Plus Bevacizumab in the Treatment of Advanced Thymoma and Thymic Carcinoma
We believe that both the EGFR pathway, as well as tumor angiogenesis play an important role
in the pathogenesis of thymic neoplasms. Our previous experience with the EGFR inhibitor
gefitinib showed a promising, though limited activity in this disease. We hypothesize that
combining the novel EGFR inhibitor erlotinib with bevacizumab will have a synergistic effect
on this tumor. We have selected the 15mg/kg q21 days of bevacizumab based on the data
published by Johnson DH et al, in which 99 patients were randomly assigned to bevacizumab
7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel
(200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). The highest
response noted in the high-dose group (31.5%) and 28.1% in the lower dose bevacizumab arm.
There was also a trend to improved TTP and OS in the high dose arm, although the study
lacked sufficient power to make any definitive conclusions regarding a possible relationship
between dose and treatment effect. (105) The safety and efficacy of this dose and schedule
was confirmed by E4599 (43). Herbst et al have confirmed the safety of the combination of
erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg in a published phase I/II trial (74)
This regimen has the potential to provide a new, effective therapy for this malignancy, as
well as teaching us important lessons about the biology of the disease. To this end, we
would also measure surrogate markers of angiogenesis, such as tumor VEGF expression, serum
VCAM-1 and bFGF, as well as urine VEGF. We would also determine tumor expression of
phosphorylated EGFR, and analyze the effect of known variant polymorphisms in the VEGF gene
on outcomes. We will test tumor samples for expression of EGFR by IHC and FISH to correlate
to response.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the objective response rate of the combination of erlotinib and bevacizumab in using RECIST.
completion of study
Patrick J Loehrer, MD
Principal Investigator
Indiana University School of Medicine
United States: Food and Drug Administration
IUCRO-0148 / 0606-20
NCT00369889
August 2006
September 2007
Name | Location |
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Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |