Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy
|Head and Neck Cancer Carcinoma, Squamous Cell Head and Neck Cancers||Drug: Lapatinib Procedure: Radiotherapy (radiation) Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5 Device: DCE-MRI||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Institutional Phase II Study of Radiation and GW572016 (Lapatinib) for Patients With Stage III-IV Head and Neck Cancer Who Cannot Tolerate Concurrent Chemoradiotherapy.|
- Progression Free Survival [ Time Frame: 2 year PFS: PFS at 2 yrs after study enrollment ]
To determine the efficacy of combining lapatinib and radiotherapy in terms of Progression-free survival (PFS) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy.
Progression-free survival is defined is the time from starting treatment to the time of first documented tumor progression or death due to any cause, which ever occurs first.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST V1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Overall Survival. [ Time Frame: Two years survival rate after study enrollment ]Overall survival is the time from starting treatment until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.
|Study Start Date:||July 2007|
|Study Completion Date:||June 2016|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: Radiotherapy and Lapatinib with DCE-MRI
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.
1500 mg po daily orally
Other Names:Procedure: Radiotherapy (radiation)
Standard of Care
Other Name: IMRT - Intensity Modulated RadiotherapyDevice: G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Standard of Care, used to deliver IMRT
Other Name: G.E. Healthcare MRI Device and SoftwareDevice: DCE-MRI
A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.
Other Name: Dynamic contrast-enhanced magnetic resonance imaging
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00490061
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, Florida|
|University of Florida Shands Cancer Center|
|Gainsville, Florida, United States, 32610|
|United States, New York|
|New York, New York, United States, 10003|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|United States, Wisconsin|
|University of Wisconsin Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Quynh-Thu Le||Stanford University|