NCT01588431

Bevacizumab/Ph 2 for Locally Advanced Head and Neck Cancer

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)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) is treated with various combinations of radiation and chemotherapy. This study aims to evaluate the rate of complete responses with induction therapy (primary endpoint) and progression-free survival, overall survival and objective response rates of docetaxel, cisplatin, cetuximab, and bevacizumab (TPE-A) followed by radiation therapy, cisplatin, cetuximab, and bevacizumab (XPE-A). 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.

Detailed description

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). Specific aims: 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. Subject population: The investigators will enroll patients with previously untreated locally advanced SCCHN (see detailed eligibility criteria). Treatment plan: Induction therapy consists of 3 cycles of bevacizumab 15mg/kg on day 1, docetaxel 75mg/m2 on day 1, loading dose of cetuximab 400mg/m2 on cycle 1, day 1, then 250 mg/m2 on all subsequent administrations (Day 8 and 15 of cycle 1 and days 1,8,15 of cycles 2 and 3), 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.

Conditions

• Carcinoma, Squamous Cell of Head and Neck

Interventions

Type	Name	Description
DRUG	Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery	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.

Timeline

• Start date: 2011-12-01
• Primary completion: 2022-10-04
• Completion: 2022-10-04
• First posted: 2012-05-01
• Last updated: 2024-02-14
• Results posted: 2024-02-14

Locations

1 site across 1 country: United States