A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy Followed By Standard Chemoradiation In HPV-Negative or High-risk HPV-Positive Locally Advanced Stage III/IVa/IVb HNSCC
To determine the maximally tolerated dose of afatinib in combination with carboplatin and paclitaxel every 21 days as an induction regimen in patients with HPV-negative stage III, IVa and IVb squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and larynx. To estimate the tumor response rate and side effects of induction chemotherapy followed by concurrent chemoradiation in patients treated with afatinib.
-confirmed diagnosis of squamous cell carcinoma, HPV-negative or p16-negative, stage III and IVa-b of oral cavity, oropharynx, hypopharynx, and larynx -measurable disease -no prior therapy for this cancer -good physical condition with good blood counts and organ function -disease-free of any prior malignancy for at least 2 years -no prior radiation above the clavicles -no gastrointestinal tract disease resulting in an inability to take or absorb oral or enteral medication -no baseline significant gastrointestinal symptoms with diarrhea as a major symptom -no active infection, symptomatic or unstable cardiac disease -patients with prior cardiac disease may require evaluation by a cardiologist prior to study entry
Afatinib, an oral medication which inhibits the erbB-family tyrosine kinase receptors EGFR and HER2, will be taken daily beginning 2 weeks prior to the start of induction therapy with 2 cycles of paclitaxel and carboplatin. Each cycle is 21 days and afatinib will continue to be be taken daily during the cycles. Concurrent chemoradiation will then be given for 7 weeks with cisplatin given weekly during the course of radiation. Response to treatment will be evaluated 12 weeks following the end of radiation.
12/20/2013 04:02 AM