Adjuvant Cetuximab and Chemoradiation in Head and Neck Cancer (ACCRA-HN)
This multicenter, open-label, uncontrolled phase II trial evaluates safety and efficacy of post-operative chemoradiation in combination with cetuximab in squamous cell carcinoma of the head and neck.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter, Open-label Phase II Trial on Post-surgery Chemoradiation in Combination With Cetuximab in Squamous Cell Carcinoma of the Head and Neck With High Risk of Locoregional Recurrence.|
- Rate of patients experiencing grade 3/4 acute toxicities not considering grade 3/4 skin tox. outside the radiation portals combined with 2-years disease-free survival rate. [ Time Frame: any toxicities occurring within 90 days post radiation start ] [ Designated as safety issue: Yes ]
- Incidence of Loco-regional relapse [ Time Frame: assessment after patient has completed follow-up ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: time from start of surgery to the first evidence of loco-regional or distant tumor relapse or death ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: from start of surgery to the first observation of disease progression or death ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: censored at the time of last documented efficacy ] [ Designated as safety issue: No ]
- The rate of patients with secondary primary neoplasm [ Time Frame: assessment after patient has completed follow-up ] [ Designated as safety issue: Yes ]
- The incidence of late toxicity [ Time Frame: beyond 90 days after start of radiation therapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2008|
|Estimated Study Completion Date:||September 2014|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Cetuximab in combination with radiotherapy, cisplatin and 5-FU. After chemoradiotherapy all patients receive a cetuximab maintenance therapy.
Loading dose prior to chemoradiotherapy 400 mg/m², followed by every week infusion of 250 mg/m² during chemoradiotherapy. After chemoradiotherapy every 2 week infusions of 500 mg/m² over 6 months.
Other Name: Erbitux
Advanced squamous cell carcinoma of the head and neck still has a poor prognosis and loco-regional recurrence frequently occurs. Efforts have been made to improve response rates and survival and different therapeutic regimens including concurrent chemo-radiotherapy or sequential chemo-radiotherapy have been developed.
To further increase the outcome of patients with locally advanced SCCHN effective new treatments with minimal toxicities are needed. Molecular targeted agents, which do not demonstrate overlapping toxicities with commonly used chemotherapy agents, have therefore been investigated. The EGFR is widely expressed at high levels in SSCHN and is associated with poor prognosis.
Cetuximab has already been investigated in combination with radiotherapy or chemotherapy in patients with head and neck cancer. The immunoradiotherapy was well tolerated with most of the side effects related to the high dose irradiation. The most common side effects are mucositis and dysphagia. Additionally, skin reactions appear sometimes more frequently in cetuximab administration. Grade 3 to 4 infusion reactions were observed in 3% of the patients treated with cetuximab. Based on the current promising results with RCT in patients with locally advanced head and neck cancer and clinical results with EGFR-antibodies plus RT, the present study was primarily designed to define the acute grade 3/4 toxicity.
We expect to show effective results in reducing the risk of distant metastasis, with administration of an additional six month adjuvant cetuximab treatment, in patient with recurrent SCCHN.
|Department of Radiotherapy and Radiological Oncology, University Hospital Munich|
|Munich, Bavaria, Germany, 81377|
|Department of Radiotherapeutics of the University Hospital Freiburg|
|Freiburg, BW, Germany, 79106|
|Department of Radiological Oncology University Hospital Heidelberg|
|Heidelberg, BW, Germany, 69120|
|Department of Radiotherapy and Radiological Oncology University Hospital Tuebingen|
|Tuebingen, BW, Germany, 72076|
|Department of Radiotherapy and Radiological Oncology University Hospital Ulm|
|Ulm, BW, Germany, 89091|
|Department of Radiotherapy an Radiological Oncology University Hospital Essen|
|Essen, NW, Germany, 45122|
|Department of Radiotherapy and Radiological Oncology University Hospital Mainz|
|Mainz, Rheinland-Pfalz, Germany, 55131|
|Department of Radiotherapy, University Hospital Schleswig Holstein, Campus Lübeck|
|Lübeck, Schleswig Hostein, Germany, 23538|
|Department of Radiotherapy and Radiological Oncology Universität Hospital Jena|
|Jena, Thueringen, Germany, 07743|
|Charité University Medicine, Department of Radiotherapy and Radiological Oncology|
|Berlin, Germany, 13353|
|Principal Investigator:||Wilfried Budach, Prof. Dr.||Department of Radiotherapy and Radiological Oncology|