The purpose of this study is to determine the rate of response with the combination of erlotinib and bevacizumab in previously treated patients with thymoma or thymic carcinoma, and to determine potential molecular markers that may predict response to therapy in patients with thymoma or 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
iv every 21 days
oral daily
Indiana University Cancer Center
Indianapolis, Indiana, United States
To determine the objective response rate of the combination of erlotinib and bevacizumab in using RECIST.
Time frame: completion of study
To determine the time to progression of patients previously treated with thymoma and thymic carcinoma treated with the combination of erlotinib and bevacizumab.
Time frame: completion of study
To determine the toxicity of the combination of erlotinib and bevacizumab in this patient population.
Time frame: completion of study
To correlate expression of VEGF in primary tumor sample, circulating VCAM-1 and bFGF, urine VEGF levels pre-therapy with response to therapy.
Time frame: completion of study
To assess for the effect of known (functionally accepted) variant polymorphisms in the VEGF gene on outcomes.
Time frame: completion of study
To determine expression of phosphorylated EGFR receptor in tumor specimen
Time frame: completion of study
To correlate expression of EGFR by IHC and FISH with response to therapy.
Time frame: completion of study
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