Conditions: Head and Neck Cancer Carcinoma, Squamous Cell Head and Neck Cancers
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 17
Healthy volunteers: no

Brief summary:
We propose to combine lapatinib with RT alone in patients with locally advanced head and neck cancer who cannot tolerate chemotherapy. The main objective of the study is to determine the efficacy of combining concurrent radiation and lapatinib in terms of time-to-progression (TTP) in this group of patients. In addition, we will determine the 2-year locoregional control rate (LRC), progression-free survival (PFS) and overall survival (OS) in these patients. We will also evaluate the profile and frequency of late toxicity, specifically mucosal and dermatologic toxicity, of the combination of lapatinib and RT in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Detailed description:
There is substantial data to suggest that EGFR and Her-2/neu expressions are important predictors for prognosis in HNSCC. EGFR blockade with a monoclonal antibody in conjunction with radiotherapy has been shown to improve survival over radiotherapy alone in patients with locally advanced HNSCC. Dual inhibition of EGFR and ErbB2 tyrosine kinases results in greater inhibitory effect of the downstream signaling pathways in cancer cells than inhibition of either receptor alone. Phase I studies in HNSCC suggested that the drug is well tolerated when delivered either alone or concurrently with cisplatin based chemoradiotherapy in HNSCC.

We propose to combine lapatinib with RT alone in patients with locally advanced HNSCC who cannot tolerate chemotherapy. The main objective of the study is to determine the efficacy of combining concurrent radiation and lapatinib in terms of time-to-progression (TTP) in this group of patients. In addition, we will determine the 2-year locoregional control rate (LRC), progression-free survival (PFS) and overall survival (OS) in these patients. We will also evaluate the profile and frequency of late toxicity, specifically mucosal and dermatologic toxicity, of the combination of lapatinib and RT in patients with locally advanced HNSCC.

Arms:
arm 1: DCE-MRI will precede radiotherpy before and after Lapatinib loading. 1500mg/d once daily oral Lapatinib will be administration for seven days prior to and throughout radiotherapy. Radiotherapy will be delivered as Intensity Modulated Radio Therapy (IMRT) using a G.E. Healthcare 1.5T MR, systems revision 12.0 M5 for a total dose of 70Gy delivered in 2-2.12 Gy/ fraction over the course of 6.5-7 weeks.

Interventions: intervention 1: Lapatinib intervention 2: Radiotherapy (radiation) intervention 3: G.E. Healthcare 1.5T MR, systems revision 12.0 M5 intervention 4: DCE-MRI
Intervention descriptions: intervention 1: 1500 mg po daily orally intervention 2: Standard of Care intervention 3: Standard of Care, used to deliver IMRT intervention 4: A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.

Protocol document: