Pilot Study for Locally Advanced Head and Neck Cancer
Status:
Withdrawn
Trial end date:
2011-07-01
Target enrollment:
Participant gender:
Summary
Induction chemotherapy is gaining momentum in the management of locally advanced squamous
cell carcinoma of the head and neck (SCCHN). The combination of docetaxel, cisplatin, and
5-FU (TPF) was superior compared with PF in a Phase III clinical trials73,74. We have
completed a Phase II clinical trial that showed that docetaxel, cisplatin, and cetuximab
(TPE) is highly active and well tolerated as induction chemotherapy in SCCHN (Argiris et al.
ASCO 2008; A6002). Preliminary survival results are very encouraging. 39 patients were
enrolled and with median follow up 26 months the 2-year PFS was 70% and the 2-year OS 84%.The
combination of chemotherapy plus cetuximab is already a standard treatment in recurrent or
metastatic SCCHN47. Therefore, TPE can be used as the platform for the addition of novel
agents.
EGFR and VEGF are among the most important and validated molecular targets in cancer therapy.
The incorporation of novel targeted therapies to chemotherapy and radiotherapy is of
particular interest in head and neck cancer, and may improve efficacy without significantly
increasing toxicity. A Phase III trial of carboplatin/paclitaxel/bevacizumab with or without
cetuximab in advanced NSCLC has been proposed by SWOG. Bevacizumab is currently being
investigated in SCCHN with promising results. A Phase II study investigating the combination
of pemetrexed and bevacizumab (UPCI 05-002) as well as a Phase II trial of cetuximab and
bevacizumab (UPCI 05-087) in recurrent or metastatic SCCHN are ongoing at the University of
Pittsburgh with encouraging results (ASCO 2008 and ASCO 2009). In this study, 32 have been
already enrolled. There was only 1 patient with grade 3 hemorrhage. The objective response
rate is 20%, the median PFS 2.8 months and the median OS 8.1 months.
In order to further improve the efficacy of TPE and the rate of complete responses we propose
to add bevacizumab to the TPE followed by XPE regimen we developed at the University of
Pittsburgh. Due to non-overlapping toxicities and based on our prior experience we anticipate
that the regimen will be well tolerated. Moreover, we plan to obtain tumor biopsies and blood
samples in the first cycle and evaluate the modulation of biomarkers post combination
therapy. Data from induction with TPE (presented at ASCO 2009) indicate the potential
significance of cytokine levels in patient outcome. Also, we will evaluate the feasibility of
subsequent concurrent radiation, cisplatin, cetuximab and bevacizumab. Patients with stable
disease in the primary could be considered candidates to surgical resection at the discretion
of their physician, if the tumor is resectable.