Because of the advantageous activity against VEGF-C and FGF pathways and favorable toxicity profile comparing with sunitinib, the investigators plan this phase II trial of pazopanib in cisplatin-refractory recurrent or metastatic HNSCC.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
200mg/tablet, 800mg/day PO.
National Taiwan University Hospital
Taipei, Taiwan
RECRUITINGObjective 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.
Time frame: 1 year
disease control rate (CR+PR+SD),
Patients who receive at least 3 days of pazopanib will be included in the baseline, dosing and safety summaries. The primary calculation of complete response rate will be based on all response-evaluable patients.
Time frame: 1 year
Tumor Necrosis Ratio
Tumor Necrosis Ratio: On contrast enhanced T1WI, (CE-T1WI), manual delineation of the area of necrosis and entire tumor is performed on the central tumor-containing slice with the areas of necrotic center and entire tumor automatically generated. The tumor necrosis ratio is defined as the area of necrotic center over that of the entire tumor. (\<25%, \<50%, \<75%, or \>75%)
Time frame: 1 year
progression-free survival
Time frame: 1 year
overall survival
Time frame: 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.