Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Platinum-Based Chemotherapy|
- Objective response rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- disease control rate (CR+PR+SD), [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- Tumor Necrosis Ratio [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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%)
- progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Single arm study, pazopanib
200mg/tablet, 800mg/day PO.
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.
|Contact: Ruey-Long Hong, MD||+886 2 23123456 ext firstname.lastname@example.org|
|National Taiwan University Hospital||Recruiting|
|Taipei, Taiwan, 100|
|Contact: Ruey-Long Hong, MD +886 2 23123456 ext 67510 email@example.com|
|Sub-Investigator: Jo-Pai Chen, MD|
|Principal Investigator: Ruey-Long Hong, MD|
|Principal Investigator:||Ruey-Long Hong, MD||National Taiwan University Hospital|