A Phase II Study of Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Platinum-Based Chemotherapy
Pazopanib, a tyrosine kinase inhibitor targets VEGFR1/2/3, PDGFR alpha & beta, c-KIT, and
FGFR1/3 to inhibit angiogenesis. The phase II trial in advanced RCC (previous cytokine
therapy in 25 % of patients) yielded good clinical benefits (response rate 34.6%; disease
control 79.8%) with durable activity (progression-free to near 1 year) and acceptable
toxicity. The randomized phase III trial in advanced RCC are ongoing and interim analysis
revealed prolonged progression-free survival in pazopanib group compared with placebo group.
Pazopanib is an active multi-targeted tyrosine kinase inhibitor needed to broaden it new
indications to treat cancers. VEGF-C and FGF pathways are also important in the
angiogenesis, metastasis, invasion, and cancer stem cell renewal in HNSCC. Pazopanib can
also inhibit these two pathways and might offer much more suppression on tumor angiogenesis
and growth in HNSCC compared with sunitinib. Common side effects of pazopanib are grade I to
II diarrhea, hypertension, hair color change, and nausea, which are all manageable. Because
of the advantageous activity against VEGF-C and FGF pathways and favorable toxicity profile
comparing with sunitinib, we plan this phase II trial of pazopanib in cisplatin-refractory
recurrent or metastatic HNSCC.
Serum inflammation markers, like IL-6 (esp. in inflammation- mediated cancers, like virus-
related hepatocellular carcinoma and HNSCC), and host/tumor VEGF/VEGFR2 polymorphism
attracted much attention in tumor angiogenesis dependence and response prediction of
anti-angiogenesis treatments, in addition to previously described sVEGFR2 and circulating
endothelial progenitors(CEP) in the phase II trial of RCC. We will study serum
IL-6/VEGF/sVEGFR2/CEP and host/tumor VEGF/VEGFR2 polymorphism for prognosis and response
correlation.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate
Evaluable for response: From the RECIST 1.1 paper,all patients included in the study must be accounted for in the results, even if there are major protocol treatment deviations or if they are not evaluable.
1 year
No
Ruey-Long Hong, MD
Principal Investigator
National Taiwan University Hospital
Taiwan: Department of Health
201007042M
NCT01377298
June 2011
May 2014
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