A Study to Test the Safety and Efficacy of Erlotinib Plus Bevacizumab to Treat Advanced Thymoma and Thymic Cancer

Thymoma Clinical Trial

Official title: A Phase II Study of Erlotinib Plus Bevacizumab in the Treatment of Advanced Thymoma and Thymic Carcinoma

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thymic Cancer
• Thymoma
• Thymus Neoplasms

• NCT number: NCT00369889
• Study type: Interventional
• Source: Indiana University
• Status: Completed
• Phase: Phase 2
• Start date: August 2006
• Completion date: September 2007