A Phase II Study of Induction Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A) in Patients With Locally Advanced Head and Neck Cancer (CTRC# 11-36)
Locally advanced squamous cell carcinoma of the head and neck (SCCHN) is treated with
various combinations of radiation and chemotherapy. Docetaxel and cisplatin have been
combined in Phase II trials in recurrent or metastatic head and neck cancer with very
encouraging results. Induction therapy with docetaxel/cisplatin followed by
chemoradiotherapy was investigated in a randomized Phase II study in nasopharyngeal cancer
and showed superior PFS and OS in comparison with chemoradiation alone. Cetuximab is a
chimerized EGFR monoclonal antibody that has produced positive results in Phase III trials
in combination with either radiation for locally advanced disease or chemotherapy for
metastatic disease. Upregulation of vascular endothelial growth factor (VEGF) has been
associated with cetuximab resistance. Bevacizumab, an anti-VEGF antibody is currently being
investigated in SCCHN with promising results. The investigators have previously shown that
cisplatin, docetaxel and cetuximab (TPE) followed by radiotherapy, cisplatin and cetuximab
(XPE) is feasible and highly efficacious in locally advanced SCCHN (Argiris, A. et al.JCO
2011). In this Phase II study the investigators evaluate the addition of bevacizumab to
induction therapy with TPE (TPE-A) and to subsequent XPE (XPE-A).
To evaluate the rate of complete responses with induction therapy (primary endpoint) and
progression-free survival, overall survival and objective response rates. Also, the
investigators plan to investigate a panel of EGFR and angiogenesis biomarkers in pre- and
post- treatment tumor biopsies. Finally, the investigators will evaluate the associated
treatment toxicities and the quality of life.
The investigators will enroll patients with previously untreated locally advanced SCCHN (see
detailed eligibility criteria).
Induction therapy consists of 3 cycles of bevacizumab 15mg/kg on day 1, cetuximab weekly
days 1,8,15 (loading dose of cetuximab 400mg/m2 on cycle 1, day 1, then 250 mg/m2 on all
subsequent administrations), cisplatin 75mg/m2 on day 1, docetaxel 75mg/m2 on day 1,
repeated every 21 days. After 3 cycles of induction therapy, patients will receive standard
radiation 70-74 Gy/ 200 cGy/ daily, 5 days/ week with concurrent weekly cisplatin 30mg/m2,
cetuximab 250mg/m2 and bevacizumab 15mg/kg every 3 weeks x 3. There is optional surgery for
non-responders in the primary (stable disease) after TPE-A.
Statistical design and sample size:
Phase II, two-stage study with complete response rate after induction therapy as the primary
endpoint. The sample size is 33 patients.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluate the rate of complete responses with induction therapy - Change in baseline regarding treatment/tumor response after 3 cycles of chemotherapy (3months); After 8 weeks of chemo + radiation; 1 year up to 10 years. This outcome will be measured with regards to number of participants via RECIST criteria.
Athanassios Argiris, MD
University of Texas Health Science Center at San Antonio
United States: Institutional Review Board
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